Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Nanhu Brain-computer Interface Institute, Hangzhou, China.
CNS Neurosci Ther. 2024 Jun;30(6):e14800. doi: 10.1111/cns.14800.
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.
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.
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.
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.
在病理条件下，线粒体动力学的损伤被认为是神经发生减少的一个重要因素。然而，在正常发育过程中线粒体动力学、神经发生和空间记忆之间的关系尚不清楚。本研究旨在阐明在发育过程中线粒体自噬在神经发生介导的空间记忆中的作用。
使用青少年和成年雄性小鼠评估空间记忆表现。免疫荧光染色用于评估神经发生水平，通过 Western blot 和透射电子显微镜评估线粒体动力学。药理干预进一步验证了在发育过程中线粒体自噬、神经发生和行为表现之间的因果关系。
研究揭示了青少年和成年小鼠之间空间记忆的差异。与青少年相比，成年小鼠海马体中的神经发生减少，同时线粒体自噬减少。用 UMI-77 诱导成年小鼠的线粒体自噬可增强神经发生并延长空间记忆保留。相反，用 Mdivi-1 抑制青少年小鼠的线粒体自噬会导致海马体神经发生减少和空间记忆受损。
成年小鼠空间记忆的下降与线粒体自噬的减少有关，这会影响齿状回的神经发生。这突显了增强线粒体自噬以对抗与年龄或疾病相关的认知能力下降的治疗潜力。
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