Cdh1 overexpression improves emotion and cognitive-related behaviors via regulating hippocampal neuroplasticity in global cerebral ischemia rats

• DOI: 10.1016/j.neuint.2019.01.015
• Publication Date: 2019-01-21T17:42:45Z
• Authors: Bo Zhang; Xuhui Chen; Youyou Lv; Xi Wu; Lingli Gui; Yue Zhang; Jin Qiu; Guizhi Song; Wenlong Yao; Li Wan; Chuanhan Zhang
• Keywords: Male; 0301 basic medicine; Neuronal Plasticity; Emotions; Gene Expression; Cadherins; Hippocampus; Brain Ischemia; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; 0302 clinical medicine; Animals; Cognitive Dysfunction; Maze Learning

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.