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Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients

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Rao, J S, Keleshian, V L, Klein, S, Rapoport, S I·2012·Translational Psychiatry

Abstract

Alzheimer's disease (AD) and bipolar disorder (BD) are progressive brain disorders. Upregulated mRNA and protein levels of neuroinflammatory and arachidonic acid (AA) markers with loss of synaptic markers (synaptophysin and drebrin) have been reported in brain tissue from AD and BD patients. We hypothesized that some of these changes are associated with epigenetic modifications of relevant genes. To test this, we measured gene-specific CpG methylation, global DNA methylation and histone modifications in postmortem frontal cortex from BD (n=10) and AD (n=10) patients and respective age-matched controls (10 per group). AD and BD brains showed several epigenetic similarities, including global DNA hypermethylation, and histone H3 phosphorylation. These changes were associated with hypo- and hypermethylation of CpG islands in cyclooxygenase-2 and brain-derived neurotrophic factor promoter regions, respectively. Only the AD brain showed hyper- and hypomethylated CpG islands in promoter regions for cAMP response element-binding protein and nuclear transcription factor kappa B genes, respectively. Only the BD brain demonstrated increased global histone H3 acetylation and hypermethylation of the promotor region for the drebrin-like protein gene. There was no significant epigenetic modification for 12-lipooxygenase or p450 epoxygenase in either illness. Many observed epigenetic changes were inversely related to respective changes in mRNA and protein levels. These epigenetic modifications involving neuroinflammatory, AA cascade and synaptic markers may contribute to progression in AD and BD and identify new targets for drug development.

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Metadata

Authors
Rao, J. S., Keleshian, V. L., Klein, S., & Rapoport, S. I.
Venue
Translational Psychiatry
Published
2012-07-03
Volume
2
Issue
7
Pages
e132-e132
ISSN
2158-3188 (ISSN-L)
OpenAlex
W1974119296
Cited by
304
References
8
FWCI
9.29
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients. https://app.cochat.ai/papers/10.1038/tp.2012.55
The paper
Rao, J. S., Keleshian, V. L., Klein, S., & Rapoport, S. I. (2012). Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients. Translational Psychiatry. https://doi.org/10.1038/tp.2012.55

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.