Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis
| Autor: | Ruth S. Slack, Jason G. MacLaurin, Devon S. Svoboda, David S. Park, Diane C. Lagace, Mireille Khacho, Alysen Clark |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neurogenesis Mice Transgenic Mitochondrion Biology 03 medical and health sciences Mice Cognition Neural Stem Cells Genetic model Genetics Animals Humans Cognitive Dysfunction Progenitor cell Molecular Biology Genetics (clinical) Cell Proliferation Neurons Apoptosis Inducing Factor Brain Cell Differentiation Neurodegenerative Diseases General Medicine Articles Embryonic stem cell Neural stem cell Mitochondria 030104 developmental biology Stem cell Neural development Neuroscience Signal Transduction |
| Popis: | Mitochondrial dysfunction is a common feature of many genetic disorders that target the brain and cognition. However, the exact role these organelles play in the etiology of such disorders is not understood. Here, we show that mitochondrial dysfunction impairs brain development, depletes the adult neural stem cell (NSC) pool and impacts embryonic and adult neurogenesis. Using deletion of the mitochondrial oxidoreductase AIF as a genetic model of mitochondrial and neurodegenerative diseases revealed the importance of mitochondria in multiple steps of the neurogenic process. Developmentally, impaired mitochondrial function causes defects in NSC self-renewal, neural progenitor cell proliferation and cell cycle exit, as well as neuronal differentiation. Sustained mitochondrial dysfunction into adulthood leads to NSC depletion, loss of adult neurogenesis and manifests as a decline in brain function and cognitive impairment. These data demonstrate that mitochondrial dysfunction, as observed in genetic mitochondrial and neurodegenerative diseases, underlies the decline of brain function and cognition due to impaired stem cell maintenance and neurogenesis. |
| Databáze: | OpenAIRE |
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