PMID- 25820928 OWN - NLM STAT- MEDLINE DCOM- 20160829 LR - 20151023 IS - 1098-1063 (Electronic) IS - 1050-9631 (Linking) VI - 25 IP - 11 DP - 2015 Nov TI - Physical exercise and acute restraint stress differentially modulate hippocampal brain-derived neurotrophic factor transcripts and epigenetic mechanisms in mice. PG - 1380-92 LID - 10.1002/hipo.22458 [doi] AB - Physical exercise and stressful experiences have been shown to exert opposite effects on behavioral functions and brain plasticity, partly by involving the action of brain-derived neurotrophic factor (BDNF). Although epigenetic modifications are known to play a pivotal role in the regulation of the different BDNF transcripts, it is poorly understood whether epigenetic mechanisms are also implied in the BDNF modulation induced by physical exercise and stress. Here, we show that total BDNF mRNA levels and BDNF transcripts 1, 2, 3, 4, 6, and 7 were reduced immediately after acute restraint stress (RS) in the hippocampus of mice, and returned to control levels 24 h after the stress session. On the contrary, exercise increased BDNF mRNA expression and counteracted the stress-induced decrease of BDNF transcripts. Physical exercise-induced up-regulation of BDNF transcripts was accounted for by increase in histone H3 acetylated levels at specific BDNF promoters, whereas the histone H3 trimethylated lysine 27 and dimethylated lysine 9 levels were unaffected. Acute RS did not change the levels of acetylated and methylated histone H3 at the BDNF promoters. Furthermore, we found that physical exercise and RS were able to differentially modulate the histone deacetylases mRNA levels. Finally, we report that a single treatment with histone deacetylase inhibitors, prior to acute stress exposure, prevented the down-regulation of total BDNF and BDNF transcripts 1, 2, 3, and 6, partially reproducing the effect of physical exercise. Overall, these results suggest that physical exercise and stress are able to differentially modulate the expression of BDNF transcripts by possible different epigenetic mechanisms. CI - (c) 2015 Wiley Periodicals, Inc. FAU - Ieraci, Alessandro AU - Ieraci A AD - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di Milano, Milano, Italy. FAU - Mallei, Alessandra AU - Mallei A AD - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di Milano, Milano, Italy. FAU - Musazzi, Laura AU - Musazzi L AD - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di Milano, Milano, Italy. FAU - Popoli, Maurizio AU - Popoli M AD - Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and CEND, Universita degli Studi di Milano, Milano, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150415 PL - United States TA - Hippocampus JT - Hippocampus JID - 9108167 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/drug effects/*metabolism MH - Epigenesis, Genetic/drug effects/*physiology MH - Hippocampus/drug effects/*metabolism MH - Histone Deacetylase Inhibitors/*pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Motor Activity/drug effects/*physiology MH - RNA, Messenger/drug effects/metabolism MH - Restraint, Physical/*physiology MH - Stress, Psychological/*metabolism/prevention & control OTO - NOTNLM OT - BDNF exons OT - HDAC OT - hippocampus OT - restraint stress OT - running EDAT- 2015/03/31 06:00 MHDA- 2016/08/30 06:00 CRDT- 2015/03/31 06:00 PHST- 2015/03/17 00:00 [accepted] PHST- 2015/03/31 06:00 [entrez] PHST- 2015/03/31 06:00 [pubmed] PHST- 2016/08/30 06:00 [medline] AID - 10.1002/hipo.22458 [doi] PST - ppublish SO - Hippocampus. 2015 Nov;25(11):1380-92. doi: 10.1002/hipo.22458. Epub 2015 Apr 15.