PMID- 24729256 OWN - NLM STAT- MEDLINE DCOM- 20150708 LR - 20211021 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 50 IP - 3 DP - 2014 Dec TI - Epigenetic signature of chronic cerebral hypoperfusion and beneficial effects of S-adenosylmethionine in rats. PG - 839-51 LID - 10.1007/s12035-014-8698-5 [doi] AB - Chronic cerebral hypoperfusion is associated with cognitive decline in aging and age-related neurodegenerative disease. Epigenetic mechanisms are involved in the maintenance of long-term hypoxia-adapted cellular phenotypes. In the present study, the epigenetic signatures such as DNA methylation and histone acetylation, as well as S-adenosylmethionine (SAM) cycle using chronic cerebral hypoperfusion rat model were explored. Chronic cerebral hypoxia-induced global DNA hypermethylation associated with the increase of DNA methyltransferase (DNMT) 3A as well as alteration of SAM cycle. Meanwhile, an enhanced level of global histone H4 acetylation accompanied with the upregulation of histone acetyltransferase, p300/CREB-binding protein (CBP), and the downregulation of histone deacetylases (HDACs), was also observed. SAM could improve spatial capacity through the upregulation of acetylcholine and brain-derived neurotrophic factor (BDNF) rather than alteration of DNA methylation levels. In conclusion, we have demonstrated a genome-wide adjustment of DNA methylation and histone acetylation under chronic cerebral hypoxic conditions in a rat's brain. These epigenetic signatures may represent an additional mechanism to promote and maintain a hypoxic-adapted cellular responds with a potential role in memory deficits. FAU - Wu, Xiangmei AU - Wu X AD - Department of Pathology, Key Laboratory for Neurodegenerative Disease of Education Ministry, Capital Medical University, Beijing, 100069, People's Republic of China. FAU - Sun, Jing AU - Sun J FAU - Zhang, Xiaowen AU - Zhang X FAU - Li, Xiaona AU - Li X FAU - Liu, Zichen AU - Liu Z FAU - Yang, Qinglin AU - Yang Q FAU - Li, Liang AU - Li L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140412 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7LP2MPO46S (S-Adenosylmethionine) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.46 (Bace1 protein, rat) RN - EC 3.5.1.98 (Histone Deacetylases) SB - IM MH - Amyloid Precursor Protein Secretases/genetics/metabolism MH - Amyloid beta-Protein Precursor/genetics/metabolism MH - Animals MH - Aspartic Acid Endopeptidases/genetics/metabolism MH - Brain/*metabolism MH - Brain Ischemia/*drug therapy/*genetics/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - DNA Methylation MH - *Epigenesis, Genetic MH - Histone Deacetylases/metabolism MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - S-Adenosylmethionine/*therapeutic use EDAT- 2014/04/15 06:00 MHDA- 2015/07/15 06:00 CRDT- 2014/04/15 06:00 PHST- 2013/12/14 00:00 [received] PHST- 2014/03/24 00:00 [accepted] PHST- 2014/04/15 06:00 [entrez] PHST- 2014/04/15 06:00 [pubmed] PHST- 2015/07/15 06:00 [medline] AID - 10.1007/s12035-014-8698-5 [doi] PST - ppublish SO - Mol Neurobiol. 2014 Dec;50(3):839-51. doi: 10.1007/s12035-014-8698-5. Epub 2014 Apr 12.