DNA methylation as a putative mechanism for reduced dendritic spine density in the superior temporal gyrus of subjects with schizophrenia
العنوان: | DNA methylation as a putative mechanism for reduced dendritic spine density in the superior temporal gyrus of subjects with schizophrenia |
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المؤلفون: | Brandon C. McKinney, David A. Lewis, Ying Ding, Robert A. Sweet |
المصدر: | Translational Psychiatry |
بيانات النشر: | Nature Publishing Group, 2017. |
سنة النشر: | 2017 |
مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Candidate gene, Postmortem studies, Dendritic spine, Dendritic Spines, Nerve Tissue Proteins, Discs Large Homolog 1 Protein, 03 medical and health sciences, Cellular and Molecular Neuroscience, Superior temporal gyrus, 0302 clinical medicine, Cytosine nucleotide, Humans, Biological Psychiatry, Adaptor Proteins, Signal Transducing, biology, dNaM, Membrane Proteins, DNA Methylation, Middle Aged, Temporal Lobe, Psychiatry and Mental health, 030104 developmental biology, Psychotic Disorders, Case-Control Studies, DNA methylation, DLG1, biology.protein, Schizophrenia, Original Article, Female, Autopsy, Psychology, Neuroscience, 030217 neurology & neurosurgery |
الوصف: | Reduced dendritic spine density (DSD) in cortical layer 3 of the superior temporal gyrus (STG), and multiple other brain regions, is consistently observed in postmortem studies of schizophrenia (SZ). Elucidating the molecular mechanisms of this intermediate phenotype holds promise for understanding SZ pathophysiology, identifying SZ treatment targets and developing animal models. DNA methylation (DNAm), the addition of a methyl group to a cytosine nucleotide, regulates gene transcription and is a strong candidate for such a mechanism. We tested the hypothesis that DNAm correlates with DSD in the human STG and that this relationship is disrupted in SZ. We used the Illumina Infinium HumanMethylation450 Beadchip Array to quantify DNAm on a genome-wide scale in the postmortem STG from 22 SZ subjects and matched non-psychiatric control (NPC) subjects; DSD measures were available for 17 of the 22 subject pairs. We found DNAm to correlate with DSD at more sites than expected by chance in NPC, but not SZ, subjects. In addition, we show that the slopes of the linear DNAm-DSD correlations differed between SZ and NPC subjects at more sites than expected by chance. From these data, we identified 2 candidate genes for mediating DSD abnormalities in SZ: brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2) and discs large, Drosophila, homolog of, 1 (DLG1). Together, these data suggest that altered DNAm in SZ may be a mechanism for SZ-related DSD reductions. |
اللغة: | English |
تدمد: | 2158-3188 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ccbafdfc7ff60746cd4878495775bc5Test http://europepmc.org/articles/PMC5438028Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....8ccbafdfc7ff60746cd4878495775bc5 |
قاعدة البيانات: | OpenAIRE |
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