Epigenetic upregulation of corticotrophin-releasing hormone mediates postnatal maternal separation-induced memory deficiency.
Accumulating evidences demonstrated that early postnatal maternal separation induced remarkable social and memory defects in the adult rodents. Early-life stress induced long-lasting functional adaptation of neuroendocrine hypothalamic-pituitary-adrenal axis, including neuropeptide corticotrophin-releasing hormone (CRH) in the brain. In the present study, a significantly increased hippocampal CRH was observed in the adult rats with postnatal maternal separation, and blockade of CRHR1 signaling significantly attenuated the hippocampal synaptic dysfunction and memory defects in the modeled rats. Postnatal maternal separation enduringly increased histone H3 acetylation and decreased cytosine methylation in Crh promoter region, resulting from the functional adaptation of several transcriptional factors, in the hippocampal CA1 of the modeled rats. Enriched environment reversed the epigenetic upregulation of CRH, and ameliorated the hippocampal synaptic dysfunction and memory defects in the adult rats with postnatal maternal separation. This study provided novel insights into the epigenetic mechanism underlying postnatal maternal separation-induced memory deficiency, and suggested environment enrichment as a potential approach for the treatment of this disorder.
Department of Pediatrics, Qilu Hospital, Shandong Univeristy, Jinan, Shandong, P.R. China.
Aiyun
A
Wang
Department of Pediatrics, Qilu Hospital, Shandong Univeristy, Jinan, Shandong, P.R. China.
Wenying
W
Nie
Department of Pediatrics, Qilu Hospital, Shandong Univeristy, Jinan, Shandong, P.R. China.
Haixia
H
Li
Department of Pediatrics, Qilu Hospital, Shandong Univeristy, Jinan, Shandong, P.R. China.
Yuhua
Y
Hou
Department of Pediatrics, Qilu Hospital, Shandong Univeristy, Jinan, Shandong, P.R. China.
Zhen
Z
Yu
Department of Pediatrics, Qilu Hospital, Shandong Univeristy, Jinan, Shandong, P.R. China.
Qing
Q
Fan
Department of Pediatrics, Qilu Hospital, Shandong Univeristy, Jinan, Shandong, P.R. China.
Ruopeng
R
Sun
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D004558:Electric Stimulation; D044127:Epigenesis, Genetic / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006657:Histones / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008426:Maternal Deprivation; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000235:genetics* / Q000503:physiopathology; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
C101628:CP 154526; D006657:Histones; D051783:Methyl-CpG-Binding Protein 2; D011743:Pyrimidines; D011758:Pyrroles; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone