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Activation of Autophagy Ameliorates Age-Related Neurogenesis Decline and Neurodysfunction in Adult Mice

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Abstract

Adult neurogenesis is the ongoing generation of functional new neurons from neural progenitor cells (NPCs) in the mammalian brain. However, this process declines with aging, which is implicated in the recession of brain function and neurodegeneration. Understanding the mechanism of adult neurogenesis and stimulating neurogenesis will benefit the mitigation of neurodegenerative diseases. Autophagy, a highly conserved process of cellular degradation, is essential for maintaining cellular homeostasis and normal function. Whether and how autophagy affects adult neurogenesis remains poorly understood. In present study, we revealed a close connection between impaired autophagy and adult neurogenetic decline. Expression of autophagy-related genes and autophagic activity were significantly declined in the middle-adult subventricular/subgranular zone (SVZ/SGZ) homogenates and cultured NPCs, and inhibiting autophagy by siRNA interference resulted in impaired proliferation and differentiation of NPCs. Conversely, stimulating autophagy by rapamycin not only revitalized the viability of middle-adult NPCs, but also facilitated the neurogenesis in middle-adult SVZ/SGZ. More importantly, autophagic activation by rapamycin also ameliorated the olfactory sensitivity and cognitional capacities in middle-adult mice. Taken together, our results reveal that compromised autophagy is involved in the decline of adult neurogenesis, which could be reversed by autophagy activation. It also shed light on the regulation of adult neurogenesis and paves the way for developing a therapeutic strategy for aging and neurodegenerative diseases.

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Funding

This work was supported by National Natural Science Foundation of China (81200254, 81571381), Research Project Supported by Shanxi Scholarship Council of China (2020–085) and Teaching Innovation Programs of Higher Education Institutions in Shanxi (J2020094).

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  1. Na Yang and Xueqin Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy, Shanxi Medical University, 030001, Taiyuan, People’s Republic of China

    Na Yang, Xueqin Liu, Xiaojie Niu, Xiaoqiang Wang, Rong Jiang & Li Lu

  2. Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, 030001, Taiyuan, People’s Republic of China

    Na Yang & Li Lu

  3. Hematology Center of Cyrus Tang Medical Institute, Soochow University School of Medicine, 215123, Suzhou, People’s Republic of China

    Na Yuan & Jianrong Wang

  4. Institute of Advanced Materials, Nanjing Tech University, 211816, Nanjing, People’s Republic of China

    Chengwu Zhang

  5. Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore, Singapore

    Kah-Leong Lim

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  1. Na Yang
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Contributions

N.Y., XQ.L., XJ.N., XQ.W. and R.J. perfomed and analyzed the experiments. N.Y.and JR.W. helped in some animal experiments. KL. L. and L.L. conceived and designed the research. The manuscript was written by XQ. L., L.L. and CW. Z.

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Correspondence to Kah-Leong Lim or Li Lu.

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Yang, N., Liu, X., Niu, X. et al. Activation of Autophagy Ameliorates Age-Related Neurogenesis Decline and Neurodysfunction in Adult Mice. Stem Cell Rev and Rep 18, 626–641 (2022). https://doi.org/10.1007/s12015-021-10265-0

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