2. Academic Validation
  3. Hippocampal mitophagy contributes to spatial memory via maintaining neurogenesis during the development of mice

Hippocampal mitophagy contributes to spatial memory via maintaining neurogenesis during the development of mice

  • CNS Neurosci Ther. 2024 Jun;30(6):e14800. doi: 10.1111/cns.14800.
Le Xu 1 2 3,  Saboor Saeed 1 2,  Xinxu Ma 1,  Xufeng Cen 3,  Yifei Sun 1 3,  Yanan Tian 3 4,  Xuhong Zhang 1 2,  Danhua Zhang 1,  Anying Tang 1,  Hetong Zhou 1 5 6,  Jianbo Lai 1 5 6 7,  Hongguang Xia 3 4,  Shaohua Hu 1 2 5 6 7 8 9
Affiliations

Affiliations

  • 1 Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Nanhu Brain-computer Interface Institute, Hangzhou, China.
  • 3 Research Center of Clinical Pharmacy of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
  • 4 Department of Biochemistry, Zhejiang University School of Medicine, Hangzhou, China.
  • 5 The Zhejiang Key Laboratory of Precision psychiatry, Hangzhou, China.
  • 6 Brain Research Institute of Zhejiang University, Hangzhou, China.
  • 7 Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, China.
  • 8 MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University, Hangzhou, China.
  • 9 Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, China.
PMID: 38887162 DOI: 10.1111/cns.14800
Abstract

Background: Impaired mitochondrial dynamics have been identified as a significant contributing factor to reduced neurogenesis under pathological conditions. However, the relationship among mitochondrial dynamics, neurogenesis, and spatial memory during normal development remains unclear. This study aims to elucidate the role of Mitophagy in spatial memory mediated by neurogenesis during development.

Methods: Adolescent and adult male mice were used to assess spatial memory performance. Immunofluorescence staining was employed to evaluate levels of neurogenesis, and mitochondrial dynamics were assessed through western blotting and transmission electron microscopy. Pharmacological interventions further validated the causal relationship among Mitophagy, neurogenesis, and behavioral performance during development.

Results: The study revealed differences in spatial memory between adolescent and adult mice. Diminished neurogenesis, accompanied by reduced Mitophagy, was observed in the hippocampus of adult mice compared to adolescent subjects. Pharmacological induction of Mitophagy in adult mice with UMI-77 resulted in enhanced neurogenesis and prolonged spatial memory retention. Conversely, inhibition of Mitophagy with Mdivi-1 in adolescent mice led to reduced hippocampal neurogenesis and impaired spatial memory.

Conclusion: The observed decline in spatial memory in adult mice is associated with decreased Mitophagy, which affects neurogenesis in the dentate gyrus. This underscores the therapeutic potential of enhancing Mitophagy to counteract age- or disease-related cognitive decline.

Keywords

development; mitophagy; neurogenesis; spatial memory.

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