{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:58:02Z","timestamp":1790715482686,"version":"4.1.0"},"reference-count":29,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T00:00:00Z","timestamp":1544140800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China postdoctoral Science fund","award":["2017M621675"],"award-info":[{"award-number":["2017M621675"]}]},{"name":"National Natural Science Foundation of Jiangsu province","award":["BK20171280"],"award-info":[{"award-number":["BK20171280"]}]},{"name":"Six One Project","award":["LGY2017028"],"award-info":[{"award-number":["LGY2017028"]}]},{"name":"Young medical talents project","award":["QNRC2016339"],"award-info":[{"award-number":["QNRC2016339"]}]},{"name":"Natural Science Foundation of China (NSFC)","award":["81472150"],"award-info":[{"award-number":["81472150"]}]},{"name":"Shanghai Municipal Commission of Health and Family Planning, Key developing disciplines","award":["2015ZB0401"],"award-info":[{"award-number":["2015ZB0401"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Working memory impairment is a common cognitive dysfunction after traumatic brain injury (TBI), which severely affects the quality of life of patients. Acetylcholine is a neurotransmitter which is closely related to cognitive functions. In addition, epigenetic modifications are also related to cognitive functions. A neurorehabilitation strategy, enriched environment (EE) intervention, has been widely used to improve cognitive impairment. However, studies of the mechanism of EE on cholinergic system and epigenetic modifications in mouse with TBI have not been reported yet. In this paper, a mouse model with traumatic frontal lobe injury was established, and the mechanism on EE for the mice with TBI was explored. It was found that EE could improve Y-maze performance of mice with TBI, the function of cholinergic system, and the imbalance of acetylation homeostasis in the prefrontal cortex of contralateral side of TBI. In addition, EE also could increase the level of CREB binding protein and histones H3 acetylation at ChAT gene promoter region in the prefrontal cortex of contralateral side of TBI. These indicate that EE has an important effect on the improvement of working memory impairment and the underlying mechanism may involve in histones H3 acetylation at ChAT gene promoter regions in the prefrontal cortex.<\/jats:p>","DOI":"10.7717\/peerj.6113","type":"journal-article","created":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T05:12:55Z","timestamp":1544159575000},"page":"e6113","source":"Crossref","is-referenced-by-count":17,"title":["Enriched environment improves working memory impairment of mice with traumatic brain injury by enhancing histone acetylation in the prefrontal cortex"],"prefix":"10.7717","volume":"6","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, PR China"},{"name":"Department of Rehabilitation Medicine, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxiang","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jibing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfa","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2018,12,7]]},"reference":[{"key":"10.7717\/peerj.6113\/ref-1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.neuroscience.2011.12.024","article-title":"Histone deacetylase 9 as a negative regulator for choline acetyltransferase gene in NG108-15 neuronal cells","volume":"205","author":"Aizawa","year":"2012","journal-title":"Neuroscience"},{"issue":"4","key":"10.7717\/peerj.6113\/ref-2","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.neuint.2010.01.007","article-title":"Involvement of histone acetylation in the regulation of choline acetyltransferase gene in NG108-15 neuronal cells","volume":"56","author":"Aizawa","year":"2010","journal-title":"Neurochemistry International"},{"key":"10.7717\/peerj.6113\/ref-3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.brainres.2008.03.082","article-title":"Chagas\u2019 disease parasite-derived neurotrophic factor activates cholinergic gene expression in neuronal PC12 cells","volume":"1217","author":"Akpan","year":"2008","journal-title":"Brain Research"},{"issue":"4","key":"10.7717\/peerj.6113\/ref-4","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1097\/HTR.0b013e31821ebfb3","article-title":"Cholinergic dysfunction and cognitive impairment after traumatic brain injury. 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