VEGF-Mediated Cognitive and Synaptic Improvement in Chronic Cerebral Hypoperfusion Rats Involves Autophagy Process
VEGF-Mediated Cognitive and Synaptic Improvement in Chronic Cerebral Hypoperfusion Rats Involves Autophagy Process
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VEGF 介导的慢性脑灌注不足大鼠认知和突触改善涉及自噬过程
DOI：
10.1007/s12017-017-8458-6
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发表时间：
2017-08
影响因子：
3.5
通讯作者：
Ming Dong
中科院分区：
文献类型：
--
作者：
Wang Ling;Wang Jingyu;Wang Faqi;Liu Chunhua;Yang Xuening;Yang Jiajia;Ming Dong
慢性脑灌注不足（CCH）与多种以认知障碍为特征的神经退行性疾病有关。包括我们在内的数十项研究表明，外源性给药血管内皮生长因子（VEGF）可以在缺血时发挥有效的认知保护作用。然而，其潜在机制尚未得到很好的阐明。为了解决这一问题，我们探索了突触在体内的机制，因为海马突触功能对学习和记忆过程至关重要。此外，自噬在CCH条件下认知功能障碍中的作用仍存在争议。异常的自噬会威胁到突触的正常神经传递，而突触是发生大量蛋白质合成和降解的地方。因此，我们进一步研究突触功能的改变是否与自噬有关。结果表明，CCH在Morris水迷宫中对空间认知有损害。我们进一步发现，通过电生理检查和western blot检测，VEGF减轻了受损的海马突触功能，包括基础突触传递、配对脉冲促进、短期、长期可塑性、去增强以及突触蛋白水平。此外，我们的研究结果表明，CCH可以诱导过度的自噬，而VEGF可以抑制这种自噬。因此，我们推测VEGF可能通过抑制过度自噬来改善CCH诱导的突触功能受损，最终改善空间学习记忆功能。重要的是，我们的发现揭示了VEGF的潜在治疗策略。
Chronic cerebral hypoperfusion (CCH) is associated with various neurodegenerative diseases characterized by cognitive impairment. Dozens of studies including ours have indicated that exogenous administration of vascular endothelial growth factor (VEGF) could exert effective cognitive protection during ischemia. Nevertheless, the underlying mechanism has not been well clarified. To address this issue, we explored the synaptic mechanisms in vivo since hippocampal synaptic function is essential to the learning and memory process. Besides, the role of autophagy in cognitive dysfunction under conditions of CCH is still controversial. And abnormal autophagy could threaten normal neurotransmission at synapse where a large amount of protein synthesis and degradation take place. Hence, we further examined whether the altered synaptic function was associated with autophagy. The results showed that CCH impaired spatial cognition as evidenced in Morris water maze. We further found that VEGF mitigated impaired hippocampal synaptic function including basal synaptic transmission, paired-pulse facilitation, short-term, long-term plasticity, depotentiation, and the level of synaptic proteins as assessed by electrophysiological examination and western blot assay. Furthermore, our results demonstrated that CCH could induce excessive autophagy which could be inhibited by VEGF. Thus, we speculated that VEGF could ameliorate impaired synaptic function induced by CCH because of its ability to inhibit excessive autophagy, and eventually improve spatial learning and memory function. Importantly, our findings shed light on potential therapeutic strategies to be exploited in the usage of VEGF.
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影响因子：
13.3
作者：
Wang, Pei;Guan, Yun-Feng;Miao, Chao-Yu
通讯作者：
Miao, Chao-Yu
DOI：
10.1172/jci17977
发表时间：
2003-06
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Yunjuan Sun;K. Jin;Lin Xie;Jocelyn T Childs;X. Mao;A. Logvinova;D. Greenberg
通讯作者：
Yunjuan Sun;K. Jin;Lin Xie;Jocelyn T Childs;X. Mao;A. Logvinova;D. Greenberg
影响因子：
3.2
作者：
Erickson MA;Maramara LA;Lisman J
通讯作者：
Lisman J
影响因子：
11.2
作者：
X. Liang;Jie Yu;K. Brown;B. Levine
通讯作者：
X. Liang;Jie Yu;K. Brown;B. Levine
影响因子：
8.3
作者：
Jia, Yanqiu;Jin, Wei;Lv, Peiyuan
通讯作者：
Lv, Peiyuan