​Cell Journal: Restoring miRNA expression can save memory deficits in Alzheimer's disease

Alzheimer's sign is gradually becoming known to the public as a degenerative disease of the central nervous system in pre-senility and old age
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At present, there are about 6 to 8 million patients with Alzheimer's disease in China, and the prevalence rate among elderly people over 65 is about 3%-7%
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However, the cause of the disease is still unclear
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In the adult brain, neural stem cells that exist in the niche of the hippocampus nerve source maintain the function of nerve production for life
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Adult hippocampal neurogenesis (AHN) is functionally related to memory and cognitive plasticity in humans and rodents
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In Alzheimer's disease, the process of generating new neurons from the neurogenic niche of the hippocampus is hindered, but the mechanism is unclear
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On May 24, 2021, Evgenia Salta of the Netherlands Institute of Neuroscience, Bart De Strooper of the University of Leuven, Belgium, and other researchers jointly published an online publication titled "Restoring miR-132 expression rescues adult hippocampal" in the international academic journal "Cell-Stem Cell" Neurogenesis and memory deficits in Alzheimer's disease" article, the article shows that restoring the expression of miR-132 can rescue adult hippocampal neurogenesis and memory deficits in Alzheimer's disease
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DOI: 10.
1016/j.
stem.
2021.
05.
001 First, the researchers performed the proliferation of neuron progenitor cells in the subgranular region of the hippocampus dentate gyrus in tissue sections of 10 non-dementia control individuals and 10 Alzheimer’s disease patients.
Postmortem immunohistochemical analysis confirmed that adult neurogenesis was pathologically damaged in AD, and in a mouse model that the brain pathological damage in AD was confirmed to be related to the level of miR-132 in the adult hippocampal neurogenic niche
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The pathological damage of adult neurogenesis in AD is related to the level of miR-132 in the adult hippocampal neurogenic niche.
Next, the researchers evaluated the location of miR-132 in the adult neurogenic niche by fluorescence sorting technology It is confirmed that miR-132 can be recruited by adult neural stem cells and progenitor cells as part of the response to exercise or aging-related stimuli, but the same phenomenon does not appear in the hippocampal neurogenic niche when AD is pathologically damaged
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In terms of function, experiments confirmed that miR-132 is necessary for the induction of dentate gyrus neurogenesis in vivo, and can regulate neuronal differentiation in human neural stem cells and down-regulate in Alzheimer's disease-related pathology
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Adult neurogenesis requires miR-132.
Finally, the researchers explored whether increasing miR-132 levels can improve the AHN deficiency observed in Alzheimer’s disease mouse models.
Experiments show that miR-132 can alleviate Alzheimer’s disease.
The proliferation and differentiation of adult neural precursor cells in the mouse model are defective, and miR-132 can regulate late neuronal maturation in a cell-autonomous manner.
The addition of miR-132 in adult neural stem and progenitor cells can improve AD mice The dentate gyrus defect of the model
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Increasing the level of miR-132 can restore AHN-related memory deficits in aged Alzheimer's disease mice
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Experimental mechanism diagram In summary, this article has determined that miR-132 is one of the most consistently down-regulated miRNAs in AD, an effective regulator of AHN, and plays a role in cell-autonomous pre-neurogenesis in adult neural stem cells and their progeny
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The use of different Alzheimer's disease mouse models, cultured human primary and established neural stem cells, and human patient materials all prove that AHN is directly affected by the pathology of Alzheimer's disease
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The miR-132 replacement in the hippocampus of adult mice with Alzheimer's disease can restore AHN and related memory deficits
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The findings confirm the significance of AHN in a mouse model of Alzheimer's disease and reveal the possible therapeutic potential of targeting miR-132 in neurodegeneration
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