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Effects and Mechanisms of Synaptotagmin-7 in the Hippocampus on Cognitive Impairment in Aging Mice

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Abstract

Aging is an irreversible biological process that involves oxidative stress, neuroinflammation, and apoptosis, and eventually leads to cognitive dysfunction. However, the underlying mechanisms are not fully understood. In this study, we investigated the role and potential mechanisms of Synaptotagmin-7, a calcium membrane transporter in cognitive impairment in aging mice. Our results indicated that Synaptotagmin-7 expression significantly decreased in the hippocampus of d-galactose-induced or naturally aging mice when compared with healthy controls, as detected by western blot and quantitative reverse transcriptase-polymerase chain reaction analysis. Synaptotagmin-7 overexpression in the dorsal CA1 of the hippocampus reversed long-term potentiation and improved hippocampus-dependent spatial learning in d-galactose-induced aging mice. Synaptotagmin-7 overexpression also led to fully preserved learning and memory in 6-month-old mice. Mechanistically, we demonstrated that Synaptotagmin-7 improved learning and memory by elevating the level of fEPSP and downregulating the expression of aging-related genes such as p53 and p16. The results of our study provide new insights into the role of Synaptotagmin-7 in improving neuronal function and overcoming memory impairment caused by aging, suggesting that Synaptotagmin-7 overexpression may be an innovative therapeutic strategy for treating cognitive impairment.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We are grateful to Dr. Anni Jiang and Dr. Yuting Zhu for language modification.

Funding

This work was supported by grants from the National Natural Science Foundation of China (grant numbers 81471490, 81671066, and 81974162).

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Authors and Affiliations

  1. Department of Neurobiology, Institute of Brain Research, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yaru Xie, Kaining Zhi & Xianfang Meng

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  1. Yaru Xie
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  2. Kaining Zhi
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  3. Xianfang Meng
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Contributions

Yaru Xie and Xianfang Meng performed the experiments; Kaining Zhi analyzed the data; Xianfang Meng designed and supervised the study. All authors wrote the manuscript.

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Correspondence to Xianfang Meng.

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All experimental procedures were reviewed and approved by the Huazhong University of Science and Technology Ethics Committee for Care and Use of Laboratory Animals.

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Highlights

•The expression of Syt7 was decreased in the hippocampus of aging mice.

•Syt7 overexpression in CA1 improved cognitive function of mice.

•Syt7 inhibited senescence by regulating the expression of p16 and p53.

•Syt7 is a valuable target for treating neurodegenerative diseases.

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Xie, Y., Zhi, K. & Meng, X. Effects and Mechanisms of Synaptotagmin-7 in the Hippocampus on Cognitive Impairment in Aging Mice. Mol Neurobiol 58, 5756–5771 (2021). https://doi.org/10.1007/s12035-021-02528-1

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