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VEGF-Mediated Cognitive and Synaptic Improvement in Chronic Cerebral Hypoperfusion Rats Involves Autophagy Process

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Abstract

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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Acknowledgements

The study was supported by grants from the National Natural Science Foundation of China (31500865, 91520205) and Tianjin Municipal Natural Science Foundation (17JCQNJC10500). We are grateful to Professor Zhuo Yang and Tao Zhang from Nankai University for providing the technical assistance.

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Authors and Affiliations

  1. School of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin, 300072, People’s Republic of China

    Ling Wang, Jingyu Wang, Faqi Wang, Xuening Yang, Jiajia Yang & Dong Ming

  2. School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China

    Chunhua Liu

  3. State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, People’s Republic of China

    Jingyu Wang

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  1. Ling Wang
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  2. Jingyu Wang
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  5. Xuening Yang
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Correspondence to Jiajia Yang or Dong Ming.

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Wang, L., Wang, J., Wang, F. et al. VEGF-Mediated Cognitive and Synaptic Improvement in Chronic Cerebral Hypoperfusion Rats Involves Autophagy Process. Neuromol Med 19, 423–435 (2017). https://doi.org/10.1007/s12017-017-8458-6

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  • DOI: https://doi.org/10.1007/s12017-017-8458-6

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