PMID- 32846221 OWN - NLM STAT- MEDLINE DCOM- 20210430 LR - 20210430 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 737 DP - 2020 Oct 15 TI - Environmental enrichment rescues cognitive impairment with suppression of TLR4-p38MAPK signaling pathway in vascular dementia rats. PG - 135318 LID - S0304-3940(20)30588-7 [pii] LID - 10.1016/j.neulet.2020.135318 [doi] AB - Increasing evidence demonstrated the promising effects of environmental enrichment (EE) on brain recovery and cognitive performance in animal models of various diseases. However, the effect and molecular mechanisms of EE on vascular dementia (VD) remain to be studied. The aim of this study was to explore the effect of EE on cognitive decline and its mechanism. Sprague-Dawley rats underwent 2-vessel occlusion (2-VO) surgery or sham operation. Subsequently, rats were kept in EE for 4 weeks. In Morris water maze (MWM) test, we demonstrated that EE significantly improved cognitive function in rats with VD. HE staining exhibited morphological changes of neurons and quantitative analysis of TUNEL showed increased apoptotic neurons in hippocampal CA1 region following 2-VO. Results from RT-qPCR showed up-regulation of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) after 2-VO. Western blotting analysis revealed enhanced toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88) and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) in 2-VO rats. Whereas administration of EE reduced apoptotic neurons, down-regulated inflammatory factors. Moreover, EE suppressed protein expression of TLR4-p38MAPK pathway. Spearman correlation analysis showed that improved cognitive function was associated with decreased expression of TLR4 and p-p38MAPK proteins. Thus, our study proved that EE has a prominent effect on cognitive impairment and neuronal damage following 2-VO by attenuating inflammation and apoptosis, which may be realized via inhibiting the TLR4-P38MAPK signaling pathway. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Zhou, Tiantian AU - Zhou T AD - Departmenta of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. FAU - Lin, Lu AU - Lin L AD - Departmenta of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. FAU - Hao, Chizi AU - Hao C AD - Departmenta of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Electronic address: 1620759755@qq.com. FAU - Liao, Weijing AU - Liao W AD - Departmenta of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Electronic address: znsjkf@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200823 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Cytokines) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cognitive Dysfunction/*metabolism/psychology MH - Cytokines/metabolism MH - Dementia, Vascular/*metabolism/psychology MH - Disease Models, Animal MH - *Environment MH - Male MH - Phosphorylation MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/*physiology MH - Toll-Like Receptor 4/*metabolism MH - p38 Mitogen-Activated Protein Kinases/*metabolism OTO - NOTNLM OT - 2-vessel occlusion OT - Environmental enrichment OT - P38 mitogen-activated protein kinase OT - Toll-like receptor 4 OT - Vascular dementia EDAT- 2020/08/28 06:00 MHDA- 2021/05/01 06:00 CRDT- 2020/08/27 06:00 PHST- 2020/07/24 00:00 [received] PHST- 2020/08/17 00:00 [revised] PHST- 2020/08/20 00:00 [accepted] PHST- 2020/08/28 06:00 [pubmed] PHST- 2021/05/01 06:00 [medline] PHST- 2020/08/27 06:00 [entrez] AID - S0304-3940(20)30588-7 [pii] AID - 10.1016/j.neulet.2020.135318 [doi] PST - ppublish SO - Neurosci Lett. 2020 Oct 15;737:135318. doi: 10.1016/j.neulet.2020.135318. Epub 2020 Aug 23.