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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
miR-133b-3p Mitigates D-Galactose-Induced Hippocampal Neuron Aging Through Autophagy Regulation via the MAPK/ERK
Yang Cao1, Chen Zhao1, Jiaxin Li1
1Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, 150081, China.
None:
Although remarkable progress has been achieved in contemporary medical research, effective drugs or prophylactic approaches targeting neurodegenerative diseases associated with aging are still limited. Increasing evidence suggests that microRNAs (miRNAs) are closely associated with age-related neurological diseases, positioning them as novel therapeutic targets. Autophagy in neurons participates in the renewal of damaged or aged endoplasmic reticulum, mitochondria, other organelles, and aggregated proteins during aging. This study evaluated the anti-aging mechanism of miR-133b-3p in D-galactose (D-gal)-induced hippocampal neurons. A mouse aging model was established by long-term D-gal injection and compared with 18-month-old naturally aged mice to verify and confirm the successful establishment of the aging model, providing a more reliable experimental basis for exploring the changes in mechanisms during aging.Compared with young mice, the D-gal group and the 18 M group showed decreased learning and memory abilities, altered neuronal structures, downregulated miR-133b-3p expression, and inhibited MAPK/ERK signaling pathway and autophagy. In addition, in the D-gal-induced HT22 cell senescence model, autophagy was inhibited, and the expression of the age-related protein p53 was downregulated. We also found that miR-133b-3p overexpression under aging conditions can activate autophagy via the MAPK/ERK signaling pathway and exert neuroprotection in hippocampal neurons. However, the effect of miR-133b-3p in reducing cellular aging damage was weakened when the MAPK/ERK signaling pathway was blocked or autophagy was inhibited.This study revealed the significant mechanism whereby miR-133b-3p protects hippocampal neurons in aging mice. miR-133b-3p alleviates D-gal-induced cellular aging damage by activating autophagy through the MAPK/ERK signaling pathway.
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