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Akt3-mTOR regulates hippocampal neurogenesis in adult mouse
- Source :
- Journal of neurochemistryREFERENCES. 159(3)
- Publication Year :
- 2021
-
Abstract
- Akt signaling has been associated with adult neurogenesis in the hippocampal dentate gyrus (DG). We reported cognitive dysfunction in Akt3 knockout (Akt3-KO) mice with the down-regulation of mTOR activation. However, little is known about the effects of Akt3 signaling on hippocampal neurogenesis. Herein, we show that progenitor cells, neuroblasts, and mature newborn neurons in hippocampal DG expressed Akt3 protein. The Akt3 phosphorylation in hippocampal DG was increased after voluntary wheel running for 7 days in wild-type mice (running WT mice), but not in Akt3-KO mice (running Akt3-KO mice). Subsequently, we observed that the proliferation of progenitor cells was suppressed in Akt3-KO mice and the mTOR inhibitor rapamycin-treated mice, whereas enhanced in running WT mice rather than running Akt3-KO mice. Neurite growth of neuroblasts was impaired in Akt3-KO mice and rapamycin-treated mice. In contrast, neither differentiation of progenitor cells nor migrating of newly generated neurons was altered in Akt3-KO mice or running WT mice. The levels of p70S6K and 4EBP1 phosphorylation were declined in Akt3-KO mice and elevated in running WT mice depending on mTOR activation. Furthermore, telomerase activity, telomere length, and expression of telomerase reverse transcriptase (TERT) were decreased in Akt3-KO mice but increased in running WT mice rather than running Akt3-KO mice, which required the mTOR activation. The study provides in vivo evidence that Akt3-mTOR signaling plays an important role in the proliferation of progenitor cells and neurite growth through positive regulated TERT expression and activation of p70S6K and 4EBP1.
- Subjects :
- Mice, Knockout
Dentate gyrus
Neurogenesis
TOR Serine-Threonine Kinases
Ribosomal Protein S6 Kinases, 70-kDa
Biology
Hippocampal formation
Biochemistry
Cell biology
Running
Cellular and Molecular Neuroscience
Mice
Neuroblast
Gene Expression Regulation
Neural Stem Cells
Neurites
Animals
Telomerase reverse transcriptase
Progenitor cell
Protein kinase B
Proto-Oncogene Proteins c-akt
Telomerase
PI3K/AKT/mTOR pathway
Telomere Shortening
Subjects
Details
- ISSN :
- 14714159
- Volume :
- 159
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of neurochemistryREFERENCES
- Accession number :
- edsair.doi.dedup.....4cf89b9d80d8928595be59751ce30686