Damaged reward areas in human alcoholics: neuronal proportion decline and astrocyte activation
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Postmortem pathological studies described neuronal loss and reduced glial packing density in cortical areas of human alcoholics [4, 9]. We here investigated whether the proportion of neurons quantified from DNA methylation profiles, and expression of neuronal (RBFOX3 encoding NeuN protein) and reactive astrocyte (GFAP) markers are affected in the nucleus accumbens (NAc), the reward area, and, for comparison, in the dorsolateral prefrontal cortex (dlPFC) known to be damaged [4, 9] in human alcoholics.
Human frozen brain tissues of the DSM-IV alcoholics and controls, males of European descent matched for demographic and tissue parameters were obtained from New South Wales Tissue Resource Centre, University of Sydney. Genome-wide DNA methylation data for 482,421 CpGs in DNA from total tissue was profiled with Illumina Infinium HumanMethylation450 beadchip and processed using R package Cell EpigenoType Specific CETS mapper . CETSpredicts neuronal proportions from methylation levels of...
KeywordsGFAP Expression Transcriptional Dysregulation Freeze Brain Tissue Alcohol Heavy Drinking Human Alcoholic
This study was supported by Grants from the Swedish Science Research Council (K2014-62X-12190-19-5), Swedish Council for Working Life and Social Research (FAS 2009-1709) and The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas 259-2012-23). New South Wales Brain TRC was supported by The University of Sydney and the National Institute of Alcohol Abuse and Alcoholism, USA (NIH AA012725).
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed written consent was obtained from the next of kin. This study was approved by the Human Research Ethics Committees of the Sydney Local Health District, University of Sydney and the Swedish Central Ethical Review Board.
This study was funded by Swedish Science Research Council (Grant No. K2014-62X-12190-19-5), FAS (Grant No. 2009-1709) and FORMAS (Grant No. 259-2012-23).
Conflict of interest
The authors declare that they have no conflict of interest.
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