Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice
| Autor: | Theodore J. Price, Yael Kusne, Nader Sanai, Emily L. Goldberg, Wade M. Chew, Sourav Ghosh, Irina Y. Maskaykina, Heddwen L. Brooks, Kirsten H. Limesand, Sophie M. Hapak, Sara S. Parker, Janko Nikolich-Zugich |
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| Rok vydání: | 2013 |
| Předmět: |
Aging
medicine.medical_specialty Longevity Apoptosis Biology Pharmacology Hippocampus Article Mice Internal medicine medicine Animals Phosphorylation PI3K/AKT/mTOR pathway Sirolimus Stem Cells TOR Serine-Threonine Kinases RPTOR AMPK General Medicine Immunohistochemistry Neural stem cell Metformin Mice Inbred C57BL Endocrinology Systemic administration Geriatrics and Gerontology Injections Intraperitoneal medicine.drug Signal Transduction |
| Zdroj: | Age (Dordrecht, Netherlands). 36(1) |
| ISSN: | 1574-4647 |
| Popis: | The chronic and systemic administration of rapamycin extends life span in mammals. Rapamycin is a pharmacological inhibitor of mTOR. Metformin also inhibits mTOR signaling but by activating the upstream kinase AMPK. Here we report the effects of chronic and systemic administration of the two mTOR inhibitors, rapamycin and metformin, on adult neural stem cells of the subventricular region and the dendate gyrus of the mouse hippocampus. While rapamycin decreased the number of neural progenitors, metformin-mediated inhibition of mTOR had no such effect. Adult-born neurons are considered important for cognitive and behavioral health, and may contribute to improved health span. Our results demonstrate that distinct approaches of inhibiting mTOR signaling can have significantly different effects on organ function. These results underscore the importance of screening individual mTOR inhibitors on different organs and physiological processes for potential adverse effects that may compromise health span. |
| Databáze: | OpenAIRE |
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