4.6 Article

Role of Calpain-1 in Neurogenesis

Journal

FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.685938

Keywords

calpain; neurogenesis; dentate gyrus; gene expression; miRNA

Funding

  1. National Institutes of Health [R01N S104078]
  2. Daljit and Elaine Sarkaria Chair

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The study found that the absence of calpain-1 in mutant mice reduced the rate of cell proliferation and long-term survival of newly-generated neurons in the adult hippocampus. Differential gene expression related to cell division, cell migration, cell proliferation, and cell survival was identified in the brains of calpain-1 knockout mice, suggesting a significant impact on neurogenesis.
While calpains have been implicated in neurogenesis for a long time, there is still little information regarding the specific contributions of various isoforms in this process. We took advantage of the availability of mutant mice with complete deletion of calpain-1 to analyze its contribution to neurogenesis. We first used the incorporation of BrdU in newly-generated cells in the subgranular zone of the dentate gyrus to determine the role of calpain-1 deletion in neuronal proliferation. Our results showed that the lack of calpain-1 decreased the rate of cell proliferation in adult hippocampus. As previously shown, it also decreased the long-term survival of newly-generated neurons. We also used data from previously reported RNA and miRNA sequencing analyses to identify differentially expressed genes in brain of calpain-1 knock-out mice related to cell division, cell migration, cell proliferation and cell survival. A number of differentially expressed genes were identified, which could play a significant role in the changes in neurogenesis in calpain-1 knock out mice. The results provide new information regarding the role of calpain-1 in neurogenesis and have implications for better understanding the pathologies associated with calpain-1 mutations in humans.

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