Cdh1 overexpression improves emotion and cognitive-related behaviors via regulating hippocampal neuroplasticity in global cerebral ischemia rats. (March 2019)

• Record Type: Journal Article
• Authors: Zhang, Bo; Chen, Xuhui; Lv, Youyou; Wu, Xi; Gui, Lingli; Zhang, Yue; Qiu, Jin; Song, Guizhi; Yao, Wenlong; Wan, Li; Zhang, Chuanhan
• Is Part Of: Neurochemistry international. Volume 124(2019)
• Page Start: 225
• Page End: 237
• Publication Date: 2019-03
• Subjects: Anaphase-promoting complex -- Cdh1 -- Emotion -- Cognitive deficit -- Neuroplasticity -- Cerebral ischemia; APC anaphase promoting complex -- BM Barnes maze -- Cdh1 Cdc20-like protein homologue 1 -- EPM elevated plus maze -- FST forced swim test -- MWM morris water maze -- NORT novel object recognition test -- NSFT novelty suppressed feeding test -- OFT open field test -- TEM transmission electron microscope -- tGCI/R transient global cerebral ischemia reperfusion -- UPS ubiquitin proteasome system; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2019.01.015
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Post-stroke survivors exhibited cognitive deficits and performed emotional impairment. However, the effect of global cerebral ischemia on standard behavioral measures of emotionality and underlying mechanism remain largely unknown. Our previous work identified that down-regulation of Cdh1 contributed to ischemic neuronal death in rat, thus we hypothesized that Cdh1 exerts a role in emotionality after cerebral ischemia, and we investigated the effect of Cdh1 overexpression on neurogenic behaviors and possible mechanisms in transient global cerebral ischemia reperfusion (tGCI/R) rats. A series of behavioral tests were used to evaluate emotion and cognitive related behaviors, and molecular biological techniques were employed to investigate hippocampal neuroplasticity. The results showed that tGCI/R rats displayed anxiety- and depression-like behaviors and a certain degree of cognitive impairment, and these abnormal behaviors accompanied with a loss of hippocampal synapses and dendritic spines, disruption of dendrite arborization and decline in the level of GAP-43, synaptophysin, synapsin and PSD-95. However, Cdh1 overexpression improved negative emotionality, ameliorated cognitive deficits, rescued hippocampal synapses loss, prevented dendritic network disorganization, and increased the level of synaptic-associated proteins after tGCI/R. Taken together, these findings suggest that Cdh1 overexpression exerts a neuroprotective effect by regulating hippocampal neuroplasticity thus improving negative emotionality and cognitive deficits after tGCI/R. Highlights: We characterized a role of Cdh1 in the regulation of negative emotion and cognitive impairment using lentiviral vectors. Cdh1 overexpression promotes the recovery of neurological function after ischemia. Cdh1 overexpression improves anxiety- and depressive-like behaviors and ameliorates cognitive decline after ischemia. Cdh1 exerts neuroprotective effects by regulating hippocampal neuroplasticity.