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BDNF is methylated. 1000 / 2304
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sparser
"Indeed, differential methylation of the corticotropin-releasing factor gene promoter follows maternal deprivation stress, prenatal stress, and chronic mild stress. xref - xref Variation in the diet of mice during gestation or later in development can alter the methylation status of DNA in a persistent fashion. xref , xref An increase in dietary L-methionine or treatment with the nonspecific histone deacetylase inhibitor trichostatin A (TSA) reverses the effects of poor maternal care behavior on DNA methylation and hypothalamic-pituitary-adrenal axis, and behavioral responses to stress, providing further evidence that DNA methylation marks in neurons are modifiable. xref , xref Exposure to a cat increases BDNF gene methylation in the dorsal hippocampus in rats, while simultaneously favoring a decrease in methylation of the BDNF gene in the ventral hippocampus with no change in BDNF methylation in the basolateral amygdala or the prefrontal cortex. xref The functional significance of bidirectional methylation of the same gene in different brain regions, or how this is mediated, is not yet clear."
sparser
"We found in a group of patients with severe depression that BDNF exon IV CpG-87 methylation was associated with higher remission rates, meaning that patients with a methylation at BDNF exon IV CpG-87 more often became remitter than patients without a methylation at BDNF exon IV CpG-87."
sparser
"There have been many intergenerational animal studies, as well as a few human studies looking at maternal exposure as a modifier of offspring BDNF methylation, for example, studies of trauma and fear (Pilkay et al., xref ), bi‐polar disorder (Duffy et al., xref ), and depressive symptoms (Braithwaite et al., xref )."
sparser
"Dnmt mRNA alterations ( xref ), increased Bdnf DNA methylation ( xref ), and altered methylation patterns of numerous genes that play a role in neuronal growth, development, and plasticity ( xref ) have been found in the brains (within the frontal cortex, amygdala, and PVN) of individuals who committed suicide and/or had been diagnosed with major depression."
sparser
"journalCode=ynns20
Download by: [University of Wisconsin - Madison]
Date: 09 January 2018, At: 04:10
Downloaded by [University of Wisconsin - Madison] at 04:10 09 January 2018
The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the
hippocampus
Yan-Dan Hu1,2†, Wei Pang1†, Cong-Cong He3, Hao Lu2, Wei Liu1, Zi-Yu Wang1, Yan-Qiang Liu3, Cheng-Yu Huang2, Yu-Gang Jiang1
1Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China, 2Department of Nutrition and Food Hygiene, West China School of Public Health, Sichuan University, Chengdu 610041, China, 3College of Life Science, Nan Kai University, Tianjin 300000, China
Objective: This study was carried out to understand the effects of zinc deficiency in rats aged 0∼2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus."
sparser
"ELA is also associated with epigenetic modification of genes involved in neuronal plasticity, neuronal growth and neuroprotection. xref , xref Animal models of ELA show hypermethylation, and consequent downregulation of the brain-derived neurotrophic factor ( BDNF ). xref Human studies using brain tissue from suicides show that mRNAs encoding BDNF and its receptor, tropomyosin-related kinase B (TRKB), are downregulated in multiple brain regions including the prefrontal cortex and the hippocampus, and some studies report differential methylation of BDNF and TRKB in suicidal brains. xref , xref Genome-wide association studies focused on differential methylation in central and peripheral tissues of suicidal individuals having experienced ELA have identified methylation changes in genes associated with stress, cognitive processes, and neural plasticity. xref , xref This combined evidence of epigenetic regulation of suicide-related gene pathways supports the hypothesis that ELA mediates suicide risk through long-term epigenetic regulation of gene expression profiles."
sparser
"KMT2A is known as a regulator of histone H3 lysine 4 (H3K4) methylation, a histone modification enriched at promoters and enhancers, abundantly expressed throughout the brain. xref The enhanced binding of KMT2A to the brain‐derived neurotrophic factor (BDNF) promoter region 2 due to chronic morphine exposure is associated with increased H3K4me3 levels. xref BDNF is a neurotrophin widely expressed in the brain regions, including cortex, cerebellum, hippocampus and basal forebrain. xref As reported, the regulation of BDNF is essential for the pathophysiology of depression and related brain functions in which epigenetic alterations of the BDNF gene may be involved; BDNF methylation has the potential to be a biomarker of depression. xref , xref "
sparser
"One previous study of participants with borderline personality disorders ( n =115) suggested an association between poorer response to intensive dialectical behaviour therapy and increases in DNA methylation of the brain-derived neurotrophic factor gene. xref Another study of veterans with posttraumatic stress disorder ( n =16) found that higher pretreatment glucocorticoid-related NR3C1 methylation predicted treatment outcome, whereas FKBP5 gene methylation decreased across treatment time in association with recovery. xref However, some participants were also medicated in both studies."
sparser
"The results of the current study are comparable to those reported by a previous study of response to psychological therapy in borderline personality disorder, where responders and nonresponders showed a difference in the direction of change in brain-derived neurotrophic factor DNA methylation. xref "
sparser
"Analyses will characterize BDNF DNA methylation and protein levels over the recovery period and investigate this novel biomarker as a potential biological mechanism underlying the known association between childhood adversity and worse neurobehavioral outcomes following pediatric TBI."
sparser
"Prenatal and life adversities decrease the promoter IV-mediated BDNF expression via increasing its methylation [ xref , xref , xref , xref – xref ], and psychiatric disorders largely share increased BDNF promoter methylation, which can be reversed by conventional antidepressants [ xref , xref – xref ]."
sparser
"Both higher BDNF methylation ( xref , xref ) and lower BDNF protein levels ( xref – xref ) are associated with worse neurobehavioral outcomes in children with preterm birth, attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, anorexia, and autism spectrum disorder."
sparser
"A study evaluating BDNF Val66Met polymorphism methylation in the peripheral blood of healthy subjects demonstrated that the increased methylation was associated with hypoxia-related early life events and impaired working memory in Val/Val individuals, and the opposite was true for Val/Met individuals ( xref )."
sparser
"Should the targets examined fail to show correlation of BDNF methylation between peripheral biosamples (blood and saliva) and CSF or fail to show associations with childhood adversity and neurobehavioral outcomes, the establishment of the biorepository in this study will allow for many additional epigenetic biomarkers to be explored."
sparser
"Biomarkers of interest to our research questions and available for subsequent analyses will include additional BDNF methylation targets, BDNF , neurotransmitter ( xref , xref ) and inflammatory ( xref ) genotypes, and additional biomarkers related to neuroplasticity and inflammation, given their role in both childhood adversity and recovery from TBI."
sparser
"The measurement of BDNF methylation and levels from accessible biosamples may serve as an early postinjury biomarker that more accurately predicts neurobehavioral outcomes following pediatric TBI, thereby allowing for earlier identification of children at greatest risk for poor recovery and the early provision of targeted intervention."
sparser
"It is interesting to note that contrary to the finding in adults, Devlin et al. [ xref ] reported no significant effect on BDNF methylation in adolescents with ELS, whereas Dukal et al. [ xref ] reported that SLC6A4 methylation in females was significantly higher than in males, but it was not associated with ELS."
sparser
"Nutritional Neuroscience
An International Journal on Nutrition, Diet and Nervous System
ISSN: 1028-415X (Print) 1476-8305 (Online) Journal homepage: http://www.tandfonline.com/loi/ynns20
The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus
Yan-Dan Hu, Wei Pang, Cong-Cong He, Hao Lu, Wei Liu, Zi-Yu Wang, YanQiang Liu, Cheng-Yu Huang & Yu-Gang Jiang
To cite this article: Yan-Dan Hu, Wei Pang, Cong-Cong He, Hao Lu, Wei Liu, Zi-Yu Wang, YanQiang Liu, Cheng-Yu Huang & Yu-Gang Jiang (2017) The cognitive impairment induced by zinc deficiency in rats aged 0∼2 months related to BDNF DNA methylation changes in the hippocampus, Nutritional Neuroscience, 20:9, 519-525, DOI: 10.1080/1028415X."
sparser
"Interestingly, epigenetic regulations of gene transcription, in particular that of Bdnf , have been shown to have a key role in cognitive performances: a decrease in Bdnf methylation has been linked to memory enhancement in rats, suggesting that epigenetic modifications within this gene could be a crucial mechanism involved in memory consolidation. xref However, ethanol could impact BDNF-related cognition not only through epigenetic modulations but also by altering its transduction regulation."
sparser
"Using DNA from blood samples of patients with schizophrenia and healthy controls, frequency of the BDNF gene methylation was highlighted as a statistically significant relationship between patients and controls regarding decreased risk of disease in comparison to unmethylated patterns [ xref ]."
sparser
"That study continued to find that treatment with lithium or valproate was associated with lower methylation levels in BDNF exon I. Overall, the investigated regions of BDNF methylation could vary widely between the studies, making direct comparisons challenging, not to mention the methodological and analytical differences [ xref ]."
sparser
"Dnmt mRNA alterations ( xref ), increased Bdnf DNA methylation ( xref ), and altered methylation patterns of numerous genes that play a role in neuronal growth, development, and cholinergic transmission ( xref ) have been found in the brains (within the frontal cortex, amygdala, and PVN) of individuals who committed suicide and/or had been diagnosed with major depression."
sparser
"From these, 48 were selected after title and abstract screening, and only 22 studies met the inclusion criteria: i) healthy population exposed to environmental chemical contaminants, ii) case-control/cohort studies reporting BDNF protein levels, BDNF gene methylation, or SNPs of the BDNF gene, iii) articles published within 10 years, iv) free available full-text article and written in English, and v) scoring ≥7 points in the New-Castle Ottawa Scale (NOS)."
sparser
"Further, 14 of the 24 studies measured total BDNF, which refers to the measurement of both isoforms, pro- and mature BDNF, in serum, plasma, or cord blood; 4 studies evaluated the single nuclear polymorphisms of BDNF (SNP) in oral swab samples or cord blood; 3 studies the mRNA or DNA methylation of the BDNF gene in cord blood; and 1 study the mature isoform of BDNF ( xref )."
sparser
"The first study focused on assessing the relationships between bisphenol A (BPA) exposure, measured in urine when participants were 9–11 years old, with the behavioral function of participants in adolescence (15–17 years old), measured with the Child Behavior Check List (CBCL 6/18); taking into account both serum BDNF levels and BDNF gene methylation in six CpGs of Exon IV, also measured during adolescence. ( xref )."
sparser
"This study aimed to explore the preliminary effect of an evidence-based Postdischarge Developmental Support Program (PDSP) on preterm infant neurodevelopment and underlying epigenetic changes, including brain-derived neurotrophic factor (BDNF) gene-related DNA methylation and expression."
sparser
"In these patients the combined marker of early improvement and methylation status at CpG-87 decreased the sensitivity (87–60%), but increased the specificity of treatment prediction from 23 to 63% (Chi 2 = 6.9; df = 3; OR = 2.631; CI = 1.181–7.404; p = 0.031); resulting in a slightly lower OR as the single marker BDNF promoter methylation (OR: 2.96)."
sparser
"Given the intergenerational patterns of health and behavior, and previous links between childhood trauma and BDNF methylation and expression, this study investigated the potential for maternal history of traumatic experiences to influence development in her newborn, via changes in her newborn’s BDNF methylation and expression."
sparser
"For example, prior research using human blood showed increased BDNF methylation associated with increased suicidal thoughts and behavior, and a literature review considering research conducted with brain and blood tissue identified abnormal BDNF signaling as a biomarker for increased suicide risk ( xref ; xref )."
sparser
"Changes in the BDNF expression and DNA methylation level are often seen in some of the early adversity related mental diseases (e.g., depression, schizophrenia, bipolar disorder, and autism), so that BDNF DNA methylation in the blood can be used as a novel biomarker for early detection of many mental diseases ( xref )."
sparser
"Concerning carbamate and dithiocarbamate metabolites, 1-N was associated with lower BDNF serum levels [β, 95% CI: −3.91 (−7.35,-0.46)], whereas ETU was associated with more social problems [β T2 , 95% CI:3.18 (0.64,5.71)] and higher BDNF gene DNA methylation at several CpGs, concretely 2 and 3 [β T3 , 95% CI: 0.27 (0.05,0.49); 0.41 (0.15,0.67), respectively]."
sparser
"Results showed that this mixture was associated with higher withdrawn [β, p -value: 2.71, 0.05] and social [β, p -value: 4.27, <0.01] problems as well as higher BDNF DNA methylation at CpG3 [β, p -value: 2.26, <0.03], 6 [β, p -value: 0.49, 0.07], and total CpGs [β, p -value: 0.27, 0.03]."
sparser
"Notably, the observed sex-specific modulation in the correlations between BDNF methylation and K-RMET scores, along with OXTR methylation and affective ToM-PST scores, shed light on the complex biological pathways that affect social cognitive functions and their phenotypic expressions."
sparser
"Thus, the findings of this study not only align with previous research demonstrating the sex-dependent effects of BDNF methylation but also suggest that a similar sex-differentiated relationship exists between BDNF methylation and social perception in the realm of social cognition."
sparser
"In line with the preceding, there are few recent studies relating BPD and the potential epigenetic effect of psychotherapeutic treatments, specifically on BDNF gene DNA methylation (Perroud et al., xref ; Thomas et al., xref ) and APBA3 and MCF2 genes DNA methylation (Knoblich et al., xref )."
sparser
"By revealing the sex-specific pathways through which BDNF and OXTR methylation influence specific social cognitive abilities, this research advances our understanding of the biological underpinnings of social information processes and sets the stage for the development of more precise and impactful therapeutic interventions."
sparser
"Results showed that maternal BDNF methylation in saliva was positively correlated with higher levels of maternal anxiety and greater childhood exposure to domestic violence, and that brain activity measured by fMRI was positively correlated with BDNF methylation in both the anterior cingulate (ACC) and the ventromedial prefrontal cortex (vmPFC) [ xref ]."
sparser
"In a study recently discussed [ xref ], reduced BDNF mRNA expression in the PFC of adult rats exposed to maternal abuse during childhood was explained by the fact that in maltreated rats, BDNF DNA methylation (specifically, increases in BDNF exons IX and IV) lasted from infancy into adulthood."
sparser
"Notably, while BDNF promoter methylation was not correlated to motor and cognitive clinical symptoms, methylation at the three sites that showed increased levels in HD patients, was inversely correlated to HADS scores, which is a widely used self-report instrument for measuring anxiety and depression in somatically ill patients ( xref ; xref )."
sparser
"This finding is highly relevant in light of previous studies showing associations between BDNF promoter methylation in psychiatric disorders, including schizophrenia and depression, as mentioned above, with one study specifically suggesting that BDNF promoter methylation could be used as a biomarker of depression ( xref )."
sparser
"Although previous studies have reported sex differences in BDNF methylation potentially mediated by estrogen signaling ( xref ), we did not observe significant differences in methylation between females and males, however, we did see trends toward increased levels methylation at certain loci in female controls."
sparser
"Interestingly, Gadd45b knockout mice have normal levels of BDNF methylation under basal conditions, but they completely lack the enhancement of Bdnf IX and total mRNA levels caused by electroconvulsive treatment (ECT) in wildtype mice, which is accompanied by BDNF de-methylation ( xref )."
sparser
"Another study investigating the behavioural and epigenetic outcomes following administration of probiotics in Zebrafish reported changes in DNA methylation of the brain-derived neurotrophic factor (BDNF) and tryptophan 5-monooxygenase (Tph1A) genes [ xref ] which are implicated in behaviour, mood and cognition in humans [ xref , xref ]."
| PMC
sparser
"Postmortem human brain and blood studies in patients with SCZ have shown that promoter regions of several genes including REELIN , SRY-box 10 ( SOX10 ), major histocompatibility complex ( HL4 ), gluta-mate decarboxylase 1 ( GAD1 ), catechol-O-methyltransferase ( COMT ) and BDNF ( xref ; xref ; xref ; xref ; xref ) are methylated."
sparser
"Similarly, it has been demonstrated that maternal stress during pregnancy alters DNA methylation of the imprinted genes IGF2 and GNASXL in cord blood [ xref ], and that maternal stress also alters DNA methylation in NR3C1 and BDNF in buccal mucosa DNA samples obtained from 2 month-old infants born to mothers with depressive symptoms during pregnancy [ xref , xref ]."
sparser
"However, in maltreated children, the combination of BDNF Met with 5-HTTLPR s allele was associated with an increased risk for depression. xref Given that BDNF is known to exert a direct effect on neuronal growth and plasticity in hippocampus and amygdale, xref – xref it comes as little surprise to find that BDNF Val66Met × ELS interacts to predict significant changes to brain structure and function. xref Early life maltreatment in rats showed persistent changes in methylation of BDNF, altering adult BDNF gene expression in pre-frontal cortex. xref "
sparser
"The BDNF gene promotes the survival of nerve cells (neurons) and is actively involved in the growth, maturation and maintenance of these neurons, as well as in the regulation of synaptic plasticity [ xref , xref ], and methylation of BDNF leads to impaired neuronal plasticity, which may mediate the development of depression [ xref ]."
sparser
"Although no significant changes in the BDNF methylation levels at M3 in chicks after thermal conditioning and folic acid treatment were detected (left panel; P >0.05), there were significant effects of both treatments and interaction on the levels of BDNF methylation at M9 (right panel; P <0.05)."
sparser
"Infusions of Zebularine (a DNA methyltransferase inhibitor) significantly altered bdnf DNA methylation, and triggered changes in exon-specific bdnf mRNA levels, indicating that altered DNA methylation is sufficient to drive differential bdnf transcript regulation in the hippocampus."
sparser
"Since sBDNF and BDNF methylation levels have been linked to cardiovascular outcomes in previous research ( xref , xref , xref ), and there is a potential link between sBDNF and BDNF methylation levels ( xref ), it is anticipated that these two may interact to affect cardiovascular outcomes."
sparser
"Since the BDNF expression is regulated by a genetic polymorphism entailing substitution of valine by methionine at codon 66 (Val66Met) in the pro-BDNF molecule ( xref ), we compared the sBDNF level and BDNF methylation according to the presence of BDNF Val66Met polymorphism ( xref )."
sparser
"BDNF promoter 1 DNA methylation signals were also reported for unipolar major depressive disorder patients; a small number of CpG units demonstrated several fold increase or decrease in methylation in cases versus controls by mass spectrometry and subsequent hierarchical cluster analysis, generating p values smaller than 10 −11 (Fuchikami et al. xref )."
sparser
"Still, a growing number of analyses based on leukocyte-derived DNA methylation in psychiatric disorders exist, including a study of the DRD2 5′-regulatory region in sib pairs discordant for schizophrenia (Zhang et al. xref ), a functional study of the SLC12A6 promoter (Moser et al. xref ), and a methylation-sensitive representational difference analysis of lymphoblastoid cells derived from monozygotic twins noted above (Kuratomi et al. xref ), the report on BDNF methylation in unipolar depression noted above (Fuchikami et al. xref ), and the investigation of BD (D'Addario et al. xref )."
sparser
"Our results add to a growing literature on BDNF methylation in BD by the use of precise mass spectrometry assays of CpGs in previously uninvestigated BDNF promoters in one of the largest BD epigenetics samples of peripheral tissue to date; they underscore the complexity of BDNF regulation across nine functional promoters and multiple transcripts and altogether suggest a need for more comprehensive epigenetic investigation of the locus."
sparser
"Rats treated with the DNMT inhibitor AzaD showed improved motor function recovery as well as BDNF upregulation after focal ischemia. xref Also, higher BDNF promoter methylation in East Asian stroke subjects with progressive physical and cognitive decline suggests that epigenetic modifications of BDNF might be prognostic biomarkers of rehabilitation after stroke. xref BDNF has complex actions after stroke as it not only repairs damage by preventing neuronal apoptosis but also rehabilitates functional recovery by promoting neurogenesis and neuroplasticity. xref Importantly, the expression of BDNF in the post-stroke brain is known to be rapidly regulated (at 2h to 4h after reperfusion). xref , xref A preclinical study proposed the link between BDNF and PSD by showing an inverse correlation between higher depression-like behavior and decreased BDNF protein levels in male rats at 33 days after transient MCAO. xref BDNF is a well-known factor that plays a role in neuroplasticity underlying the etiology of MDD. xref Post-mortem analyses of brain tissue from suicide subjects and MDD patients showed significantly reduced levels of BDNF compared to healthy subjects. xref Accordingly, increasing BDNF levels by administrating serotonin reuptake inhibitors has been suggested as an antidepressant therapeutic mechanism in MDD. xref – xref In case of chronically stressed animals, hippocampal BDNF levels were decreased compared to unstressed controls. xref Another study showed that chronic mild stress-induced-behavioral despair was prevented in BDNF-overexpressing rats, suggesting that BDNF is a critical modulator of vulnerability to depression-like symptoms. xref Intriguingly, social defeat-induced downregulation of BDNF in the hippocampus increased methylation of histone H3 at Lys27 residue, which induced long-lasting depression-like symptoms in a chronic stress rodent model. xref In addition to histone methylation, animals with foot shock stimuli showed increased BDNF levels through upregulation of acetylation in histones H3 and H4. xref In stressed mice, the expression of hypothalamic and hippocampal BDNF was shown to be decreased, which was altered with probiotic treatment and changes in microbiota composition, respectively. xref , xref Further, systemic injection of sodium butyrate promoted histone acetylation resulting in increased BDNF levels in the frontal cortex and reduced behavioral despair in mice. xref Sodium butyrate was shown to normalize HDAC2 and BDNF levels in the hippocampus in CRS in male mice as well. xref Furthermore, sodium butyrate treatment has been found to increase BDNF expression in the brain as well as decrease BBB impairment via elevating tight junction proteins in a male mouse model of CUMS. xref Many studies highlighted the regulatory mechanisms of BDNF in providing therapeutic benefits against depression via epigenetic modifications as well as microbiota alteration. xref , xref "
sparser
"As we found deficits in BDNF gene expression within the adult prefrontal cortex specific to maltreatment, we next wanted to identify whether these patterns were correlated with lasting changes in BDNF DNA methylation, as global or site-specific methylation of CpG sites near and within regulatory regions of genes is often associated with transcriptional inactivity and gene suppression ( xref – xref )."
sparser
"To assess BDNF DNA methylation, we evaluated the region of exon IV (formerly rat exon III) encompassing the transcription start site and cyclic adenosine monophosphate (cAMP) response element, as epigenetic regulation of this particular region continues to gain support for its pivotal role in neural activity-dependent BDNF gene expression ( xref , xref , xref , xref )."
sparser
"To assess a causal relationship between maltreatment-induced changes in BDNF DNA methylation and BDNF mRNA expression in the adult prefrontal cortex, we chronically infused zebularine, a DNA methylation inhibitor, in male and female adults from our maltreatment regimen, and then assessed BDNF exon IV DNA methylation, as exon IV is the best-characterized target of epigenetic regulation of BDNF gene expression ( xref , xref , xref , xref )."
sparser
"In addition, BDNF promoter methylation was shown to be significantly correlated with the levels of alkaline phosphatase (ALP), glucose, Lp(a), ApoE and ApoA in males (ALP: r = −0.308, p = 0.042; glucose: r = −0.383, p = 0.010; Lp(a): r = 0.333, p = 0.027; ApoE: r = −0.345, p = 0.032;), ApoA levels in females (r = 0.362, p = 0.033), and C Reactive Protein (CRP) levels in both genders (males: r = −0.373, p = 0.016; females: r = −0.399, p = 0.021)."
sparser
"A systematic review of stress-associated epigenetic changes and depression found differential methylation of NRC31, SLCA4, BDNF, FKBP5, SKA2, OXTR, LINGO3, POU3F1 and ITGB1, associated with altered glucocorticoid signaling (NR3C1, FKBP5), serotonergic signaling (SLC6A4), and neurotrophin genes (BDNF)( xref )."
sparser
"Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region ( P = 0.009) and aromatase gene methylation mediates ( P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication."
sparser
"The impact of early-life EET is substantial; it can break the vicious cycle of depressed mother and promoter IV-BDNF deficiency in infants. xref , xref Early-life maltreatment of infants has been shown to increase methylation of the promoter IV-controlled BDNF DNA in the prefrontal cortex and reduce BDNF expression from infancy to adulthood. xref Consequently, abusive maternal behavior and previously acquired DNA methylation patterns perpetually transmit from generation to generation. xref Inactivation of promoter IV can also occur after exposure to toxic environments: perinatal methylmercury exposure in mice leads to DNA hypermethylation, increased histone trimethylation, and decreased histone acetylation within promoter IV in the hippocampus of offspring and was associated with depression-like behavior. xref Early detection of BDNF deficiency (for example, measuring promoter IV inactivity and related biomarkers) may help in initiating early-life EET as intervention to reduce risk of depression later in life."
sparser
"With regard to the connections among DNA methylation, prenatal exposures assessed through questionnaire and the measured anthropometric data of newborns (highlighted by green cycles in xref ), the most interesting connections were observed between environmental exposures during pregnancy and the methylation levels of the MGMT gene in the maternal buccal mucosa (SA = 0.94), between stressful events and both BDNF methylation in the maternal buccal mucosa (SA = 0.94) and NR3C1 methylation in the placenta (SA = 0.98), and between H19 gene methylation in the placenta and suboptimal birth weight (binding strength = 0.94)."
sparser
"Altered methylation of the BDNF gene was found in the placental tissue, in the umbilical cord and venous blood of women who suffered traumatic events during pregnancy [ xref ], while altered methylation of the NR3C1 gene was found in the DNA extracted from the umbilical cord of newborns born to depressed mothers [ xref ]."
sparser
"A complex network involving amygdala and neurotrophin regulation emerges from studies in mice where changes in Bdnf methylation pattern were found during contextual fear learning (Suri et al , xref ), and from studies showing dysfunctions in amygdala and neurotrophin levels in neuropsychiatric disorders such as schizophrenia and depression (Nurjono & Chong, xref ; Kuhn et al , xref )."
sparser
"Crucially, we identify synergistic cross-scale interactions through specific nodal points—exemplified by BDNF methylation simultaneously enhancing spinal cord long-term potentiation while disrupting prefrontal-limbic circuitry to exacerbate negative affect, forming self-reinforcing pathological loops."
sparser
"DNA methylation, may contribute to the embedding of maternal distress into emotional outcomes. xref , xref Nazzari reported that higher maternal antenatal anxiety was associated with greater negative emotionality of infant, and further contributed to methylation of the BDNF gene in male infants but not in female infants."
sparser
"As evidence for increased BDNF methylation contributing to borderline personality disorder symptoms, individuals who responded positively to intensive dialectical behavior therapy exhibited reduced BDNF methylation after completing their treatment regimen relative to their methylation levels prior to treatment ( xref )."
sparser
"Besides epigenetic alternations of the NR3C1 gene, an association of BDNF genotype and promoter methylation with acute and long-term stroke outcomes was also found in an East Asian cohort.[ xref ] Many studies suggested that BDNF plays an important role in regulating energy homeostasis and body weight.[ xref , xref ] Pereira and colleagues found that FKBP5 gene expression in subcutaneous adipose tissue was correlated to markers of insulin resistance.[ xref ] These studies provide an important illustration that expression of HPA axis related genes altered by an epigenetic mechanism may contribute to susceptibility to cardiometabolic disease, and posit a possible mechanism underlying the link between childhood adversity and cardiometabolic risk."
sparser
"We found that the protein expression of DNMT1 was decreased and DNMT3a and DNMT3b mRNA or/and protein levels were increased, which indicated that DNMTs plays a role in BPS-induced neurotoxicity in mice and leads to abnormal methylation of the BDNF gene, finally affecting protein synthesis."
sparser
"As studies testing the BDNF system across molecular levels are sparse, this study aimed at investigating the BDNF val66met genotype, BDNF DNA methylation changes and peripheral BDNF serum levels in acute and remitted phases of MDD (major depressive disorder) and BD (bipolar disorder) and healthy controls."
sparser
"Interestingly, a recent human study found that not only gestational stress but also the history of trauma suffered by the mother was associated with epigenetic regulation of Bdnf in their newborns (Bdnf methylation and BDNF protein expression measured from umbilical cord blood after birth)."
sparser
"Our finding is in keeping with recent studies on the relationship between methylation status, such as that of BDNF and SLC6A4 , and post-stroke depression, which have consistently reported an association between higher methylation status and depression, although the strength of these associations differs slightly according to the time elapsed after stroke. xref xref However, it is not known whether the influence of BDNF methylation differs according to the time elapsed after breast surgery, and this issue may require further research."
sparser
"This finding is consistent with our recent study on the relationship between BDNF methylation and post-stroke depression, which similarly found no interaction between BDNF methylation and its genotype. xref However, other previous research on the association between SLC6A4 methylation and depression found that SLC6A4 methylation status was dependent on its genotype and consequently had interactive effects on depression. xref xref xref Considering these results, further research on the relationship between BDNF methylation and genotype should be conducted in a broader range of populations."
sparser
"A few groups have shown the way in this regard, notably (Roth et al., xref ), who found that chronic psychosocial stress after predator exposure, a model of PTSD, produced a significant increase in DNA methylation of the BDNF gene in the dorsal hippocampus while a decrease was seen in the ventral sub-region."
sparser
"Taken in context with the established ELA related behavioral vulnerabilities that BDNF methylation alterations represent, blood BDNF expression and methylation levels could potentially be of clinical use as a tool in clinical care of psychopathologies such as MDD, when coupled with the presentation of symptoms and a reported history of ELA ( xref )."
sparser
"Additional evidence of this non-genomic transmission comes from rodent studies of the effects of postnatal abuse and suggests that environmentally induced modification to methylation of the exon IV region of the BDNF gene can be inherited by offspring and grand-offspring through variations in the perinatal mother–infant interaction (Roth et al., xref )."
sparser
"89.14 ± 13.30 83.17 ± 10.09 49.05 ± 7.92*†
The effects of zinc deficiency on DNMT1, DNMT3A, and DNMT3B mRNA expression To determine whether the increase in the BDNF methylation were due to the activity changes of DNA methyltransferases (DNMTs), the mRNA levels of DNMT1, DNMT3A, and DNMT3B were measured by semiquantitative PCR."
sparser
"Their work also revealed the positive associations between changes of global efficiency and methylation of RELN and BDNF genes ( xref ), which provided an integrated macro- and microscopic perspective of the neuroplastic mechanisms underlying cognitive impairments in schizophrenic individuals, and linked the associations among DNAm, brain structural connectivity, and cognitive function in this disease."
sparser
"For example, increased miR-16 expression ( xref ) and increased promoter DNA methylation of BDNF ( xref ) were found in separate studies, but both changes result in a reduction in brain derived neurotropic factor (BDNF) mRNA expression, suggesting BDNF may play a role in regulating offspring behavior in response to prenatal stress exposure."
sparser
"However, it is not known how BDNF methylation status influences BDNF secretion over time after stroke, and it is important to bear in mind that there were no significant genotype-methylation interactions ( xref ) and no direct associations between BDNF genotype and methylation percentages ( xref ) in our sample."
sparser
"We find that females exhibit changes in Bdnf methylation that very rarely match male patterns. xref , xref , xref We also observe significant, brain-region specific differences in genome-wide DNA methylation and hydroxymethylation in adversity-exposed adolescent males, an effect not observed in females. xref These alterations are accompanied by sex-specific deficits in select behavioral tasks, xref data which support the hypothesis that altered epigenetic patterns are behaviorally functional."
sparser
"This is consistent with a previous study where individuals with higher neuroticism scores (or lower emotional stability) had higher levels of brain-derived neurotrophic factor gene methylation compared with those with lower neuroticism (or higher emotional stability) scores. xref More studies are needed to examine the mechanisms linking chronic pain, epigenetics and characteristics such as personality traits in aging."
sparser
"In a mouse model of early stress, Avp hypomethylation was detected at 6 weeks of age and persisted up to the last measurement at 1 year of age. xref In a similar model, Pomc hypomethylation is maintained within the same time frame. xref In contrast to these sustained marks, our lab has found developmental changes in methylation of the Bdnf gene in our adversity-exposed rats."
sparser
"In infancy, we find that adversity-exposed females exhibit a brain region-specific decrease in methylation of Bdnf exon I alongside increased methylation of exon IV, the reverse of which is then found in adulthood. xref In males, the only developmental change detected in Bdnf methylation is at exon I in adolescence. xref Not only is that mark found to be reversed (i.e. opposite direction in methylation) in adulthood, six additional alterations in Bdnf methylation emerge at this time point. xref , xref Additionally we find several significant, maltreatment-specific alterations in epigenetic regulators in the mPFC of our adult animals that are not detected in infancy. xref Taken together, these data underline the importance of longitudinal studies of environmental effects upon the epigenome, a type of study that is somewhat lacking in the field at present."
sparser
"Antidepressants may increase BDNF promoter methylation and perform divergent actions, compared with mood stabilizers. xref , xref Animal experiments have shown that the dynamic expression of BDNF is related to the methylation of CpG island dinucleotides in the mouse BDNF gene. xref A number of studies have shown that the concentration of BDNF in the peripheral blood is reduced in patients with depression, and animal experiments have shown that methylation of CpG in exon IV is significantly lower in the hippocampus, where BDNF is expressed at high levels, than in the cerebral cortex and striatum, which have low levels of BDNF expression. xref , xref Previous studies have found that there is a significant internal correlation between the methylation levels of exon I of the BDNF gene in the brain, peripheral blood and muscle tissue. xref The BDNF gene and 5‐HT neurons can interact with each other, regulate each other and maintain a certain dynamic balance."
sparser
"A follow-up pilot study in an existing European cohort “the Childhood and Environment (INMA)-Granada cohort” confirmed that higher childhood urinary BPA concentrations were associated with higher peripheral blood BDNF DNA methylation at adolescence, and that BDNF methylation mediated 34% of the longitudinal association between BPA exposure and behavioural problems ( xref )."
sparser
"By using schizotypy as the proxy for genetic-based liability to schizophrenia and methylation of brain-derived neurotrophic factor (BDNF) to represent environmental exposure, this study investigated the impact of the interaction between vulnerability and the environment on the neurobiological substrates of schizophrenia."
sparser
"However, some reports have suggested that the methylation of BDNF exon I may be a biomarker of the response to electroconvulsive therapy. xref We analysed the correlation between the level of BDNF gene methylation and HAMD factor scores in the depression group before sertraline treatment."
sparser
"Thus, the objectives of this study were (1) to investigate changes in resting-state brain network FC in UHR individuals compared with healthy control (HC) individuals and (2) to evaluate the moderating effect of schizotypy on the relationship between BDNF methylation on network FC."
sparser
"In regards to the DMN-FPN network FC, the novel challenge of this study was to examine the statistical interaction between the level of schizotypy and BDNF methylation to determine whether vulnerability and environmental influence have a joint impact on the underlying neurobiological mechanism of schizophrenia."
sparser
"In the case of BDNF methylation on brain activity related to schizophrenia, one study xref found that BDNF methylation in healthy individuals was associated with prefrontal cortex functional activity and working memory accuracy, which was used as an index of phenotypes relevant to schizophrenia."
sparser
"Our findings and previous research xref suggest that BDNF methylation can bridge the environmental exposures to the endophenotypes of schizophrenia; however, caution is required when interpreting hypothetical linkages between BDNF methylation and brain network changes in schizophrenia due to the scarcity research."
sparser
"With this precaution, the moderation effect of schizotypy on the positive association between BDNF methylation and network FC indicates that dampening of this positive association in individuals with high levels of schizophrenia liability may result in reduced DMN-FPN network FC in individuals at high risk for schizophrenia who show elevated levels of schizotypy."
sparser
"A recent study also reported no significant difference in mean methylation of BDNF among first-episode psychosis individuals, their unaffected siblings, and healthy controls; however, the study found higher levels of methylation in individuals with childhood trauma independent of diagnosis xref ."
sparser
"At peripubertal stage, there again are prominent effects of prenatal exposure to EDCs in male rat offspring, such as changes in expression and DNA methylation of BDNF (brain-derived neurotrophic factor) after prenatal bisphenol A exposure ( xref ), but gene expression changes have also been observed in female hippocampus at that stage, specifically, genes related to serotonin turnover, after the same treatment ( xref )."
sparser
"Adult mice experiencing chronic defeat stress reveal a lasting increase in histone H3-K27 methylation at the P3 and P4 BDNF promoter sites, associated with decreased hippocampal BDNF exon III and IV mRNA. xref Epigenetic chromatin and DNA changes following stress mediate enduring changes in BDNF production."
sparser
"Studies in schizophrenia show that RELN hypermethylation reduces reelin expression and disrupts synaptic plasticity and neuronal migration; COMT methylation alters dopamine metabolism; and BDNF methylation is associated with cognitive impairment and negative symptoms ( xref , xref )."
sparser
"First, a number of genes are associated with depressive disorders, such as variations in the 5-HTT serotonin transporter gene and polymorphisms in the STin2.12 allele [ xref ]; SNPs [ xref ]; clock-controlled genes (CCGs) driven by endogenous molecular clocks that regulate rhythmic expression [ xref ]; SLC6A4, COMT, TPH2, FKBP5, MDD1, HTR2A, and MDD2 as well as methylation in genes BDNF, NR3C1, and OXTR [ xref ]; the CCN gene family with elevated CCN2 and CCN3 expression [ xref ]; deletion of the STS gene [ xref ]; methyl transferase-like 13; chromosomal locations 16p13 and 8q24 [ xref ]; mRNA expression of 5α-reductase type I [ xref ], and PRS folate metabolism (MTHFR C677T) [ xref ]."
sparser
"Studies in PTSD and suicidality demonstrate that early-life trauma is associated with long-lasting BDNF promoter methylation, affecting stress reactivity and fear extinction, and for suicide victims, BDNF promoter hypermethylation is observed in the prefrontal cortex and hippocampus ( xref – xref )."
sparser
"In terms of specific research evidence, Guo J et al. ( xref ) conducted a study on 164 PTSD patients and 141 healthy controls and found that not only were the serum BDNF levels of PTSD patients significantly higher than those of the control group, but the methylation level of their BDNF promoter was also significantly higher; Lee HS et al. ( xref ) further observed in 99 PTSD patients and 81 healthy controls that there was an interaction between traumatic experience and epigenetic methylation of BDNF, especially that childhood trauma exposure may have a long-term impact on the methylation status of BDNF; Guo JC et al. ( xref ) conducted a study on 322 PTSD patients and 215 controls and directly showed that stressful events may be an important inducer of methylation of CpG sites in the BDNF promoter region of PTSD patients; similarly, Kim TY et al. ( xref ) conducted a study on 126 veterans and 122 healthy controls and found that compared with those without PTSD, the methylation level of BDNF promoter in PTSD patients was significantly higher than that in PTSD patients without PTSD."
sparser
"In the high-IL-18 group, but not in the low-IL-18 group, a higher average BDNF methylation level was associated with increases in composite MACEs (HR (95% CI) = 2.15 (1.42–3.26)), all-cause mortality (HR (95% CI) = 1.89 (1.11–3.22)), myocardial infarction (HR (95% CI) = 1.98 (1.07–3.67)), and percutaneous coronary intervention (HR (95% CI) = 1.81 (1.01–3.23)), independent of confounding variables."
sparser
"A lower CpG methylation level within the regulatory domain of the Bdnf gene is related to increased BDNF synthesis in neurons [ xref ], and a higher BDNF methylation level has been linked to composite major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS) [ xref ]."
sparser
"By subjecting the first generation of rats to maternal separation and the subsequent generation raised in a balanced cross-fostering manner, it was found that early-life stress through maternal separation resulted in increased Bdnf methylation in both male and female rats, but Bdnf expression was reduced only in females ( xref )."
sparser
"The 34 studies showed that AD cases, compared to controls, have a higher degree of methylation of OPRK1 , UQCRC1 , AR , BDNF and HTERT in blood cells, BDNF , synaptophysin gene, CREB promoters, APOE , TREM 2 , TBX2AR , SORBS3 and SPTBN4 in the brain, and lower methylation levels of 2-5a-synthetase gene in skin fibroblasts, PIN1 , FAAH , ALOX5 and DR4 gene in blood cells, TNFA , COX-2 , NF-kβ gene and S100A2 and CRTC1 in the brain tissue."
sparser
"Methylation in the promoter region of the serotonin transporter (SLC6A4) gene determined from peripheral DNA has been reported to interact with SLC6A4 genotype to predict depressive symptoms in adolescents; xref brain derived neurotrophic factor ( BDNF ) methylation profiles derived from peripheral blood cells have been found to correctly classify patients with major depressive disorder, xref and preliminary data suggest promoter associated methylation of the FK506 binding protein 5 ( FKBP5 ) gene mediates the combined effect of genetic (e.g., FKBP5 high-risk polymorphisms) and environmental (e.g., child abuse) risk for stress related psychiatric disorders. xref Increased promoter associated glucocorticoid receptor ( NR3C1) gene methylation in the hippocampus has also been associated with suicide completion in individuals with a history of early child abuse in two independent studies. xref , xref Suicide completers without a history of childhood abuse did not have increased methylation of the NR3C1 gene when compared to controls, suggesting depression-associated methylation profiles may be different in depressed individuals with and without a history of early adversity. xref , xref "
sparser
"The development of fear generalization, a core clinical feature of PTSD, is also closely related to the epigenetic regulation of BDNF: Lubin FD et al. ( xref ) found in a rat model that during the consolidation of fear memory, BDNF DNA methylation and chromatin remodeling jointly regulated the expression of BDNF mRNA in the hippocampus."
sparser
"The Illumina 450K Beadchip includes 16 CpG sites in SLC6A4 , 77 sites in BDNF , 41 sites in NR3C1 and 34 sites in FKBP5 , and xref , available online contains the results of analyses examining methylation in candidate genes SLC6A4 , BDNF , NR3C1 , and FKBP5 as predictors of children’s depression scores."
sparser
"We observed that the switch to a WD increased Bdnf methylation specific to exon IV, in proportion to anxiety-like behavior, in Sprague Dawley rats reared in low omega-3 fatty acid diet, and these effects were abolished by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine."
sparser
"Predator-induced fear has also been associated with changes in DNA methylation. xref found that higher Dlgap2 methylation was associated with predator odor exposed rodents. xref documented multigenerational DNA methylation associations, finding that the female offspring of mice exposed to predator odor during pregnancy have decreased methylation of BDNF in the hippocampus."
sparser
"Though functionally significant and experience-dependent epigenetic regulation of Bdnf has been established in the brain and in some peripheral tissue ( xref ; xref ; xref ; xref ; xref ; xref ; xref ; xref ), this is the first report to our knowledge that examines the relationship between Bdnf methylation in the developing spinal cord and motor behavior."
sparser
"Consequently, this suggests that peripheral BDNF or TrkB levels and other associated factors, such as the role of TrkB isoforms, BDNF promoter methylation, BDNF-AS, and the BDNF pro-to-mature-domain ratio, may be used as biomarkers for early disease detection, risk, mnemonic symptoms, and conversion."
sparser
"Patients struggling with the disease show a decreased expression of BDNF and AcH3K14 genes and an increased expression of histone deacetylases in the hippocampus [ xref ], as well as elevated levels of methylation of the promoter region of exon 1 in the BDNF gene compared to controls [ xref ]."
sparser
"Roth TL et al. ( xref ) confirmed that after adult rats were exposed to social and psychological stress stimulation, they developed symptoms similar to those of PTSD patients, and this stimulation significantly increased BDNF DNA methylation in the dorsal hippocampus of rats, among which the BDNF DNA methylation intensity was the highest in the dorsal CA1 subregion."
sparser
"This result clarified the regional specificity of BDNF epigenetic modification, and such changes in BDNF DNA methylation in the hippocampus may lead to persistent damage to hippocampal function, and this damage may persist for several years after emotional trauma in PTSD patients ( xref )."
sparser
"Fransquet et al. PD et al. (56) also confirmed in their study of 118 mothers of torture victims in Kosovo and their offspring that after adjusting for covariates, methylation of multiple genes involved in HPA axis regulation was associated with cortisol levels, among which three CpG sites of BDNF (cg27193031, cg25328597 and cg04672351) were significantly associated with cortisol levels, suggesting that PTSD during pregnancy plays a role in mediating abnormal cortisol signaling in offspring, and is partially regulated by BDNF DNA methylation ( xref )."
sparser
"High cortisol can further promote BDNF promoter methylation by activating DNA methyltransferase DNMT3A (for every 10 nmol/L increase in cortisol concentration, BDNF methylation increases by 7.3%), forming a vicious cycle of “NR3C1 methylation → increased cortisol → BDNF methylation → decreased neuroplasticity”."
sparser
"In leukocyte-adjusted analyses of loci in 32 obesity-related candidate genes ( xref ), significant associations were found between BDNF gene-wide methylation and group ( xref ; p=5.3E-5, significance passing Bonferroni threshold of α=0.05/32, or p<0.0016, accounting for 32 genes)."
sparser
"In another two athletes, we examined burnout and chronic biomarkers from hair and blood (hair cortisol, glycated haemoglobin [HbA1c], triglycerides, total cholesterol, high-density lipoprotein cholesterol, and DNA methylation in the BDNF, SLC6A4, and NR3C1 genes) in six samples over 12 months."
sparser
"This suggests that increased levels of peripheral BDNF promoter methylation may be an epigenetic biomarker indicating the transformation of aMCI to AD ( xref ). xref examined the DNA methylation levels of the COASY and SPINT gene promoter regions and found that DNA methylation in the two regions was significantly increased in AD and aMCI as compared to controls. xref found that global DNA methylation in the peripheral blood mononuclear cells of LOAD patients was higher compared to healthy controls, and higher DNA methylation levels were associated with the presence of APOE ᵰ04 allele ( p = 0.0043) and APOE ᵰ03 carriers ( p = 0.05) in the global population."
sparser
"For example, Okada ( xref ) found in depressed individuals that the level of promoter methylation of the 5-HTT gene ( SLC6A ) predicted magnitude of response to therapy, and BDNF methylation status could be a proxy marker for previous suicidal attempts and a clinical biomarker for poor treatment outcomes of suicidal ideation in depression ( xref )."
sparser
"Following exposure to maltreatment, animals of both sexes exhibit increased DNA methylation of the brain-derived neurotrophic factor ( Bdnf ) gene in whole prefrontal cortex as well as altered levels of various epigenetic regulators in the medial prefrontal cortex (mPFC) ( xref ; xref )."
sparser
"Elevated miR-34 expression after trauma and BDNF promoter methylation exhibit a “dual inhibitory” effect—miR-34 not only directly degrades BDNF mRNA but also promotes its methylation by upregulating DNMT3B. Additional data on the strength of the correlation between the two is needed (e.g., a r=0.63 between miR-34 expression and BDNF methylation levels) to clarify the “amplifier” role of non-coding RNA in regulating BDNF methylation."
sparser
"Fuchikami et al. [ xref ] found that DNA methylation of the BDNF gene can be used as a biomarker for differentiating healthy controls from patients with depression due to different methylation levels of CpG units within CpG I of the BDNF gene between healthy controls and patients with depression."
sparser
"At the behavioral level, the latency of fear memory extinction in rats in the 2 mg/kg dose group was shortened by 43%, and the frequency of hypervigilance behavior was reduced by 38%, directly confirming that DNMT inhibitors improve the core symptoms of PTSD by correcting BDNF methylation ( xref )."
sparser
"In individuals with mild cognitive impairment (MCI) and dementia, we have investigated BDNF Val66Met genotype distribution, peripheral BDNF DNA methylation, mRNA and protein levels, and cognitive performance using the Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT)."
sparser
"The only available human-related data are cross-sectional observational results—BDNF promoter methylation levels in peripheral blood of PTSD patients are significantly higher than those in healthy controls—but this result only confirms the association between BDNF methylation and human PTSD, without verifying intervention efficacy."
sparser
"Here we investigated the role of DNA methylation of the brain-derived neurotrophic factor (Bdnf) gene in the therapeutic effects of ketamine in combination with extinction training in a mouse model of post-traumatic stress disorder (PTSD) induced by inescapable electric foot shocks (IFS)."
sparser
"Emerging evidence indicates a bidirectional interaction between BDNF Val66Met polymorphism and DNA methylation: the Met allele may predict hypo- or hypermethylation within exon IX and at distant promoters, potentially shaping individual susceptibility to cognitive decline [ xref , xref ]."
sparser
"More recently, a significant interaction was noted between traumatic experience and epigenetic methylation of BDNF and a possible moderating effect of the OT receptor gene rs53576 in a group of healthy controls, while suggesting that the OT gene may influence epigenetic mechanisms [ xref ]."
sparser
"Methylation analysis in a subset of a total of 200 patients (114 patients with dementia, of whom 31 had severe cognitive impairment, and 86 patients with MCI) revealed that the differences in methylation of 6 chosen regions in BDNF promoters and exon IX were not statistically significant between individuals with dementia and MCI ( xref , xref )."
sparser
"In PTSD-related studies, this technology has clarified the unique regulatory pattern of BDNF methylation in microglia: contrary to the trend of reduced expression caused by high methylation of BDNF in neurons, the methylation level of BDNF in microglia of PTSD patients is significantly reduced, and this change is closely related to the active DNA demethylation process mediated by TET2 ( xref )."
sparser
"The CRISPR-dCas9-based epigenetic editing system, by fusing the nuclease-inactive Cas9 protein with methylation regulatory factors (such as demethylases), can achieve precise regulation of the methylation status of specific gene sites, providing technical support for the targeted correction of abnormal BDNF methylation ( xref )."
sparser
"Multiple linear regression revealed that there was a significant positive correlation between percent of methylation in the BDNF_IV2 region and scores on the CDT scale ( p = 0.019, xref ), while the MMSE scale did not show significant association with methylation in the BDNF gene."
sparser
"Finally, the Mendelian randomization analyses relied on a small number of mQTLs (3 for epilepsy to BDNF methylation and 1 for methylation to epilepsy and other health outcomes) and therefore did not allow for sensitivity analyses aimed at ruling out bias due to horizontal pleiotropy."
sparser
"The transmission of paternal trauma depends on tsRNA (tRNA-derived small RNA) in sperm: trauma exposure leads to changes in the expression profile of specific tsRNA in paternal sperm, among which the level of tsRNA related to BDNF methylation regulation (such as tsRNA-Arg-CCG) is significantly increased; this tsRNA enters the egg during fertilization and indirectly leads to hypermethylation of the BDNF promoter by regulating the activity of DNA methyltransferases (such as DNMT3A) in the hippocampus of the offspring embryo, ultimately affecting BDNF expression and PTSD susceptibility in the offspring ( xref , xref )."
sparser
"The discovery of this transgenerational genetic effect expands the temporal dimension of BDNF methylation in PTSD research, suggesting that the prevention and control of PTSD may need to consider parental trauma history and reduce the risk of intergenerational transmission of the disease through early intervention of BDNF methylation abnormalities in parents or offspring."
sparser
"This study has several limitations, with the core contradiction being the mismatch between research objectives and evidence sources—while the core goal of this study is to focus on the regulatory mechanisms and intervention value of BDNF DNA methylation in human PTSD populations, the key mechanistic arguments and intervention efficacy evidence currently rely heavily on animal experimental studies, with relatively scarce human-derived data."
sparser
"As our previous work reports, increased methylation at this exon of Bdnf in the PFC is a stable epigenetic change across the lifespan that occurs in response to early maltreatment, thus giving us a suitable starting point to investigate pharmacological prevention of maltreatment-induced epigenetic marks."
sparser
"Given previously mentioned data from our lab demonstrating increased Bdnf methylation following adversity, and taking into account that HDAC activity is higher in adversity-exposed brains ( xref ) and Bdnf is a gene altered by sodium butyrate ( xref ; xref ; xref ; xref ), we chose to employ this HDAC inhibitor to investigate the feasibility of preventing aberrant epigenetic marking of the Bdnf gene in the adversity-exposed brain."
sparser
"Thus, the current study examines Bdnf exon IX methylation in the male and female PFC of developing animals following exposure to nurturing or adverse care during the first week of life, and the ability of the HDACi sodium butyrate to prevent the previously reported, adversity-induced increase in methylation at this locus."
sparser
"Abnormally regulated BDNF DNA methylation was explored in a rodent temporal lobe epilepsy model, and was shown to have a dual role in modulating both epileptiform abnormalities and memory impairments. xref , xref Memory consolidation is an important mechanism supporting long-term memory that may also be disrupted by epileptiform activity."
sparser
"This indicated that BDNF Val66Met polymorphism might have differential effects on cognitive functions in the presence of psychopathology and could modulate the effect of age and severity of psychiatric disorders on cognitive performance, possibly through BDNF methylation [ xref , xref , xref ]."
sparser
"This is in line with the study which reported the association of BDNF Val66Met polymorphism and DNA methylation at surrounding CpG sites in frontal cortex brain tissue [ xref ] and the general theory that nearby CpG sites are commonly methylated together, possibly due to the preference of DNA methyltransferases to methylate CpG pairs at a particular distance range or due to the influence of neighboring CpG sites in the recruitment of DNA methylase and/or demethylase enzymes [ xref ]."
sparser
"These transcripts could contribute to BDNF alterations that are reported in several psychiatric conditions and could also be modulated by successful pharmacological treatments. xref , xref , xref , xref The high expression of BDNF exon IV is particularly intriguing, as its promoter region is well investigated in term of epigenetic regulation, which may sustain long-lasting changes in its expression (see the below paragraph for details on BDNF DNA methylation)."
sparser
"For example, when compared with controls, a significant increase in DNA methylation at BDNF promoter IV was found in the Wernicke area from suicide subjects and, interestingly, this higher methylation pattern correlated with lower mRNA levels for BDNF transcript IV. xref An increase in DNA methylation levels of this BDNF promoter region was reported in association with lower BDNF protein levels in the prefrontal cortex of elderly people. xref Furthermore, higher DNA methylation levels were also found in the prefrontal cortex of valine/valine homozygous subjects, as compared with metionine (Met) carriers, suggesting an association between BDNF genotype and DNA methylation. xref The notion that epigenetic changes are associated with variations in DNA sequence may underlie, at least in part, the inconsistencies of genetic-association studies in psychiatric disorders."
sparser
"BDNF is a direct molecular target of MeCP2, xref and reduced BDNF protein levels (~50%–70% of wild type, depending on brain region) were found in adult MeCP2 KO animals. xref Importantly, reduced levels of BDNF protein was also found in human postmortem RTT tissue relative to age-matched controls. xref Early researches utilizing in vitro techniques demonstrate that upon neuronal depolarization, BDNF expression is normally increased through at least two MeCP2-dependent mechanisms: 1) decreased CpG methylation of Bdnf , decreasing its interaction with the MeCP2-histone deacetylase-mSin3A repression complex and increasing Bdnf transcription, xref and 2) Ca 2+ -dependent phosphorylation of MeCP2, decreasing its repression of Bdnf expression. xref These studies indicate that Bdnf expression is controlled by MeCP2; therefore, some of the deficits observed in RTT may be due to loss of BDNF."
sparser
"In a previous study, a strong correlation between gestational bisphenol A (BPA) exposure and brain-derived neurotrophic factor ( BDNF ) DNA methylation in the umbilical cord blood was observed in the children from Columbia Center for Children’s Environmental Health cohort ( xref )."