title: Enriched environment improves post-stroke cognitive impairment in mice by potential regulation of acetylation homeostasis in cholinergic circuits.
abstract: Post-stroke cognitive impairment (PSCI), commonly seen in the clinical practice, is a major factor impeding patient rehabilitation. Enriched environment (EE) intervention is a simple and effective way to improve cognitive impairment, partially due to the rebalancing of the basal forebrain-hippocampus cholinergic signaling pathway. Epigenetic changes have been identified in many cognitive disorders. However, studies on the effects of EE on epigenetic regulation of cholinergic circuits in PSCI animal models have not yet been reported. In this study, we established a photothrombotic mouse PSCI model and showed that after EE intervention, mice with PSCI had significantly improved water maze performance, better induction of hippocampal long-term potentiation (LTP), enhanced function of the basal forebrain-hippocampus cholinergic circuits of contralateral side of stroke and relatively balanced acetylation homeostasis compared to those of PSCI mice in standard environments (SE). In addition, PSCI mice in EE expressed much higher levels of p-CREB and CBP than in SE, and the chromatins bound to M-type promoter of ChAT gene were more acetylated. These results demonstrate that EE plays an important role in the improvement of PSCI and the underlying mechanism may involve in the acetylation of histones bound to the ChAT gene promoter in cholinergic circuits.
authors.affiliation: Department of Neurological Rehabilitation, WuTaiShan Hospital of Yangzhou University, Yangzhou, PR China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou, PR China; Non-coding RNA Center, Yangzhou University, Yangzhou, PR China. Electronic address: wx000805qm@yeah.net.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Physical Education, Yangzhou University, Yangzhou, PR China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Basic Medical Science & Technology, Yangzhou University, Yangzhou, PR China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neurology, Nanjing BenQ Hospital, Nanjing, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of Basic Medical Science & Technology, Yangzhou University, Yangzhou, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry, WuTaiShan Hospital of Yangzhou University, Yangzhou, PR China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Basic Medical Science & Technology, Yangzhou University, Yangzhou, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, WuTaiShan Hospital of Yangzhou University, Yangzhou, PR China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Non-coding RNA Center, Yangzhou University, Yangzhou, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.affiliation: Non-coding RNA Center, Yangzhou University, Yangzhou, PR China.
authors.forename: Feiyang
authors.initials: F
authors.lastname: Shen
authors.affiliation: College of Rehabilitation Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China. Electronic address: shanclhappy@163.com.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Shan
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou, PR China; Non-coding RNA Center, Yangzhou University, Yangzhou, PR China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, PR China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, PR China. Electronic address: duonan@yahoo.com.
authors.forename: Duonan
authors.initials: D
authors.lastname: Yu
mesh_terms: D000107:Acetylation; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D018678:Cholinergic Agents / Q000627:therapeutic use; D059329:Cholinergic Neurons / Q000502:physiology*; D002843:Chromatin; D003072:Cognition Disorders / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000628:therapy*; D004195:Disease Models, Animal; D004777:Environment; D044127:Epigenesis, Genetic; D006624:Hippocampus / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D020521:Stroke / Q000378:metabolism / Q000628:therapy*
chemical_list: D018678:Cholinergic Agents; D002843:Chromatin; D006657:Histones; D000109:Acetylcholine
keywords: CREB binding protein (CBP); Choline acetyltransferase; Enriched environment; Histone acetylation homeostasis; Phosphorylated cAMP response element binding protein (p-CREB); Post-stroke cognitive impairment