The effects of pH on DNA methylation state: In vitro and post-mortem brain studies

2008 ◽  
Vol 174 (1) ◽  
pp. 123-125 ◽  
Author(s):  
Carl Ernst ◽  
Patrick O. McGowan ◽  
Vesselina Deleva ◽  
Michael J. Meaney ◽  
Moshe Szyf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Post Mortem ◽  
Methylation State ◽  
Post Mortem Brain ◽  
Effects Of Ph

scholarly journals LINE-1 and Alu methylation Signatures in Autism Spectrum Disorder and Their Function in The Regulation of Autism-Related Genes

2021 ◽  
Author(s):  
Thanit Saeliw ◽  
Tiravut Permpoon ◽  
Nutta Iadsee ◽  
Tewin Tencomnao ◽  
Tewarit Sarachana ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Autism Spectrum ◽  
Small Sample ◽  
Spectrum Disorder ◽  
Post Mortem ◽  
Global Methylation ◽  
Post Mortem Brain ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

Abstract BackgroundLong interspersed nucleotide element-1 (LINE-1) and Alu elements are retrotransposons whose abilities cause abnormal gene expression and genomic instability. Several studies have focused on DNA methylation profiling of gene regions, but the locus-specific methylation of LINE-1 and Alu elements has not been identified in autism spectrum disorder (ASD).MethodsHere, DNA methylation age was predicted using Horvath’s method. We interrogated locus- and family-specific methylation profiles of LINE-1 and Alu elements (22,352 loci) in ASD blood using publicly-available Illumina Infinium 450K methylation datasets from heterogeneous ASD (n = 52), ASD with 16p11.2 del (n = 7), and ASD with Chromodomain Helicase DNA-binding 8 (CHD8) variants (n = 15). The differentially methylated positions of LINE-1 and Alu elements corresponding to genes were combined with transcriptome data from multiple ASD studies. ROC curve was conducted to examine the specificity of target loci.ResultsEpigenetic age acceleration was significantly decelerated in ASD children over the age of 11 years. DNA methylation profiling revealed LINE-1 and Alu methylation signatures in each ASD risk loci by which global methylation were notably hypomethylated exclusively in ASD with CHD8 variants. When LINE-1 and Alu elements were clustered into subfamilies, we found methylation changes in a family-specific manner in L1P, L1H, HAL, AluJ, and AluS families in the heterogeneous ASD and ASD with CHD8 variants. Our results showed that LINE-1 and Alu methylation within target genes is inversely related to the expression level in each ASD variant. Moreover, LINE-1 and Alu methylation signatures can be used to predict ASD individuals from non-ASD.LimitationsIntegration of methylome and transcriptome datasets was performed from different ASD cohorts. The small sample size of the validation cohort used post-mortem brain tissues and necessitates future validation in a larger cohort.ConclusionsThe DNA methylation signatures of the LINE-1 and Alu elements in ASD, as well as their functional impact on ASD-related genes, have been studied. These findings are considered for further research into DNA methylation profiles and the expression of the LINE-1 and Alu elements in post-mortem brain tissue, which has been linked to ASD pathogenesis.

scholarly journals DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Simona Keller ◽  
Daniela Punzo ◽  
Mariella Cuomo ◽  
Ornella Affinito ◽  
Lorena Coretti ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Post Mortem ◽  
Post Mortem Brain

scholarly journals Reactive astrocytes augment hippocampal inhibitory tone via GABA transporter-3/4 to facilitate synaptic balance in Alzheimer’s disease

2021 ◽  
Author(s):  
Yousif Aldabbagh ◽  
Anam Islam ◽  
Weicong Zhang ◽  
Paul Whiting ◽  
Afia Ali
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tonic Inhibition ◽  
Reactive Astrocytes ◽  
Post Mortem ◽  
Wild Type ◽  
Gaba Transporter ◽  
Synaptic Excitation ◽  
Post Mortem Brain

Background and Purpose: Cognitive decline is a major symptom in Alzheimer’s disease (AD), which is closely associated with synaptic excitatory-inhibitory imbalance. Here, we investigated whether astrocytic mechanisms involving the astrocyte-specific GABA transporter 3/4 (GAT3/4) play a role in altering the synaptic balance in AD and whether these mechanisms correlate with presynaptic cannabinoid type-1 receptors (CB1-Rs). Experimental approach: Using the APPNL-F/NL-F knock-in mouse model of AD, aged-matched to wild-type mice, we performed in vitro electrophysiological whole-cell recordings combined with immunohistochemistry in the CA1 and dentate gyrus (DG) regions of the hippocampus. Comparative neuroanatomy experiments were also performed in post-mortem brain tissue from human AD patients, age-matched to healthy controls. Results: We observed a higher expression of GABA content and GAT3/4 co-localised with reactive astrocytes, which enhanced tonic inhibition in the CA1, and DG of APPNL-F/NL-F mice compared to the age-matched wild-type animals. Blocking GAT3/4 - associated tonic inhibition in APPNL-F/NL-F mice resulted in an enhanced frequency of synaptic excitation, suggesting a presynaptic mechanism. These data also correlated with an up-regulation of CB1-Rs in astrocytes and cholecystokinin (CCK)-containing interneurons, which also enhanced tonic inhibition in the AD model, but did not affect GAT3/4 -associated tonic inhibition. The neuroanatomical results were mirrored in post-mortem tissue of AD patients. Conclusions: Our data suggest that reactive astrocytes lead to augmented tonic inhibition in the hippocampus, which probably plays an important presynaptic compensatory role in attempting to restore AD-associated neuronal hyperactivity. Therefore, reducing tonic inhibition through GAT3/4 may not be a good therapeutic strategy for AD.

SA68SUICIDE-ASSOCIATED DNA METHYLATION CHANGES IN POST-MORTEM BRAIN SAMPLES: A META-ANALYSIS

2019 ◽  
Vol 29 ◽  
pp. S1225
Author(s):  
Stefania Policicchio ◽  
Joana Viana ◽  
Artemis Iatrou ◽  
Eilis Hannon ◽  
Joe Burrage ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Meta Analysis ◽  
Post Mortem ◽  
Post Mortem Brain

scholarly journals DNA methylation and histone post-translational modification stability in post-mortem brain tissue

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Jessica S. Jarmasz ◽  
Hannah Stirton ◽  
James R. Davie ◽  
Marc R. Del Bigio
Keyword(s):  
Dna Methylation ◽  
Brain Tissue ◽  
Post Mortem ◽  
Post Translational Modification ◽  
Post Mortem Brain

SA64DIFFERENTIAL DNA METHYLATION OF GDAP1 AND HECW2 IN POST MORTEM BRAIN SAMPLES AND IN A RAT MODEL FOR ALCOHOL DEPENDENCE

2019 ◽  
Vol 29 ◽  
pp. S1222-S1223
Author(s):  
Ariane Wiegand ◽  
Vanessa Gräf Olmos ◽  
Wolfgang H. Sommer ◽  
Anita C. Hansson ◽  
Vanessa Nieratschker
Keyword(s):  
Dna Methylation ◽  
Alcohol Dependence ◽  
Rat Model ◽  
Post Mortem ◽  
Post Mortem Brain

scholarly journals Tissue-specific DNA methylation of the human prodynorphin gene in post-mortem brain tissues and PBMCs

2010 ◽  
pp. 1 ◽  
Author(s):  
Vadim Yuferov ◽  
David A. Nielsen ◽  
Orna Levran ◽  
Matthew Randesi ◽  
Sara Hamon ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Post Mortem ◽  
Tissue Specific ◽  
Post Mortem Brain ◽  
Brain Tissues

scholarly journals Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthew Devall ◽  
Rebecca G. Smith ◽  
Aaron Jeffries ◽  
Eilis Hannon ◽  
Matthew N. Davies ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Brain Tissue ◽  
Regional Differences ◽  
Post Mortem ◽  
Post Mortem Brain

scholarly journals Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging

2021 ◽  
Vol 15 ◽  
Author(s):  
Tanpreet Kaur ◽  
Allen F. Brooks ◽  
Alex Lapsys ◽  
Timothy J. Desmond ◽  
Jenelle Stauff ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Imaging Modality ◽  
Brain Slices ◽  
Post Mortem ◽  
Molar Activity ◽  
Positron Emission ◽  
Post Mortem Brain

Mutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein (mHTT), which is the hallmark pathology of neurodegenerative Huntington’s disease (HD). Development of a high affinity 18F radiotracer would enable the study of Huntington’s disease pathology using a non-invasive imaging modality, positron emission tomography (PET) imaging. Herein, we report the first synthesis of fluorine-18 imaging agent, 6-(5-((5-(2,2-difluoro-2-(fluoro-18F)ethoxy)pyridin-2-yl)methoxy)benzo[d]oxazol-2-yl)-2-methylpyridazin-3(2H)-one ([18F]1), a radioligand for HD and its preclinical evaluation in vitro (autoradiography of post-mortem HD brains) and in vivo (rodent and non-human primate brain PET). [18F]1 was synthesized in a 4.1% RCY (decay corrected) and in an average molar activity of 16.5 ± 12.5 GBq/μmol (445 ± 339 Ci/mmol). [18F]1 penetrated the blood-brain barrier of both rodents and primates, and specific saturable binding in post-mortem brain slices was observed that correlated to mHTT aggregates identified by immunohistochemistry.

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