Akt3-mTOR regulates hippocampal neurogenesis in adult mouse.
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.
['Zhang|Tingting|T|', 'Ding|Hong|H|', 'Wang|Ya|Y|', 'Yuan|Zihao|Z|', 'Zhang|Yajie|Y|', 'Chen|Guiquan|G|', 'Xu|Yun|Y|', 'Chen|Ling|L|0000-0003-4557-8511']
D000818:Animals D005786:Gene Expression Regulation D051379:Mice D018345:Mice, Knockout D058953:Neural Stem Cells D016501:Neurites D055495:Neurogenesis D051057:Proto-Oncogene Proteins c-akt D038762:Ribosomal Protein S6 Kinases, 70-kDa D012420:Running D058570:TOR Serine-Threonine Kinases D019098:Telomerase D059506:Telomere Shortening
neurogenesis Akt3 telomerase mammalian target of rapamycin (mTOR)