The role of PSD95-mediated synaptogenesis in hypoxic-induced neurobehavioral impairment in mice
10.16557/j.cnki.1000-7547.2025.05.006
- VernacularTitle:PSD95介导的突触发生在低氧诱导小鼠神经行为损伤中的作用
- Author:
Yang ZHOU
1
;
Yi SHI
1
;
Ruili GUAN
1
;
Chong XUE
1
;
Kailun YU
1
;
Xuefeng SHEN
1
Author Information
1. 空军军医大学军事预防医学系军队劳动与环境卫生学教研室暨特殊作业环境危害评估与防治教育部重点实验室,陕西省环境健康危害评估与防护重点实验室,西安 710032
- Publication Type:Journal Article
- Keywords:
hypoxia;
neurobehavior;
synapses;
dendritic spine;
postsynaptic density-95(PSD95);
mouse
- From:
Chinese Journal of Neuroanatomy
2025;41(5):591-598
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of PSD95 on neurobehavioral abnormalities and synaptic damage in cortex induced by hypoxia exposure in mice.Methods:The 3-week-old C57BL/6 male mice were injected with neuron-specific adeno-associated virus through stereotaxic brain after 7 days of normal environment adaptation.The mice were divided into normoxia group(AAV-NC-Nor),control hypoxia group(AAV-NC-Hyp),normal oxygen group with over-expression of postsynaptic density-95(PSD95)(AAV-PSD95-Nor),and hypoxia group with over-expression of PSD95(AAV-PSD95-Hyp).Using a hypobaric hypoxia chamber,PSD95-overexpressing mice were continuously ex-posed to hypoxic conditions for 14 days to establish a hypoxia exposure model.The open field,elevated cross maze and conditioned fear tests were used to detect the neurobehavioral activities of mice,and Golgi staining was used to observe the density of neuronal dendritic spines in cortex.The expression of PSD95,SYN1 and N-methyl-D-aspartate receptor subtype 2A(NMDAR2A)were detected by Western blot.Result:Compared with the normal oxygen group,the total distance and average speed of exercise in the open field experiment of mice in hypoxia group increased(P＜0.01),the rigidity time of mice in the conditioned fear box decreased(P＜0.01),and the density of dendritic spines in cortical region decreased(P＜0.05).The expressions of PSD95,SYN1 and NMDAR2A were decreased(P＜0.05).After the over-expression of PSD95,the autonomic activity of mice was reduced,the fear memory was relieved(P＜0.05),the dendrite density was reversed(P＜0.05),and the expression of synaptic related protein was increased(P＜0.05).Conclusion:Over-expression of PSD95 can alleviate neurobehavioral abnormalities and decline of fear memory induced under hypoxia exposure,protect neuronal dendritic spine injury in cortical region,and up-regulate the expression of syn-aptic protein.
