Age- and sex-dependent effects of metformin on neural precursor cells and cognitive recovery in a model of neonatal stroke
| Autor: | Rebecca M. Ruddy, Cindi M. Morshead, Kelsey V. Adams |
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| Rok vydání: | 2019 |
| Předmět: |
Male
endocrine system diseases Cellular differentiation Neurogenesis Subventricular zone Biology 03 medical and health sciences Mice 0302 clinical medicine Neural Stem Cells Cell Movement Precursor cell otorhinolaryngologic diseases medicine Animals Hypoglycemic Agents Progenitor cell Neonatal stroke Research Articles 030304 developmental biology Neurons 0303 health sciences Multidisciplinary digestive oral and skin physiology nutritional and metabolic diseases SciAdv r-articles Cell Differentiation medicine.disease Neural stem cell Metformin Mice Inbred C57BL Stroke stomatognathic diseases Disease Models Animal medicine.anatomical_structure Animals Newborn Female Signal transduction Cognition Disorders Neuroscience 030217 neurology & neurosurgery medicine.drug Signal Transduction Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Metformin expands the neural precursor pool in adult females, but not males, and is correlated with cognitive recovery. Resident neural stem and progenitor cells, collectively termed neural precursor cells (NPCs), reside in a well-defined neurogenic niche in the subventricular zone (SVZ) and contribute to ongoing postnatal neurogenesis. It is well established that the NPC niche can alter the behavior of NPCs. NPC activation is a promising therapeutic strategy for brain repair. The drug metformin has been shown to activate neural stem cells, promote differentiation, and lead to functional motor recovery in a neonatal stroke model. We demonstrate that metformin-induced NPC expansion and functional recovery is sex hormone dependent. Metformin increases the size of the NPC pool in adult females, but not males, and promotes cognitive recovery in a model of brain injury in females, but not males. Our data demonstrate that metformin has age- and sex-dependent effects on NPCs that correlate with functional recovery, which has important implications for neural repair. |
| Databáze: | OpenAIRE |
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