Research Group Adult Neurogenesis and Neural Stem Cells, Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Munich-Neuherberg, Germany, Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany, and F. Hoffmann-La Roche Ltd, CNS Discovery, Pharma Research and Early Development, CH-4070 Basel, Switzerland.
J Neurosci. 2014 May 7;34(19):6624-33. doi: 10.1523/JNEUROSCI.4972-13.2014.
Neural stem cells in the adult mammalian hippocampus continuously generate new functional neurons, which modify the hippocampal network and significantly contribute to cognitive processes and mood regulation. Here, we show that the development of new neurons from stem cells in adult mice is paralleled by extensive changes to mitochondrial mass, distribution, and shape. Moreover, exercise-a strong modifier of adult hippocampal neurogenesis-accelerates neuronal maturation and induces a profound increase in mitochondrial content and the presence of mitochondria in dendritic segments. Genetic inhibition of the activity of the mitochondrial fission factor dynamin-related protein 1 (Drp1) inhibits neurogenesis under basal and exercise conditions. Conversely, enhanced Drp1 activity furthers exercise-induced acceleration of neuronal maturation. Collectively, these results indicate that adult hippocampal neurogenesis requires adaptation of the mitochondrial compartment and suggest that mitochondria are targets for enhancing neurogenesis-dependent hippocampal plasticity.
成年哺乳动物海马体中的神经干细胞持续产生新的功能性神经元,这些神经元修饰海马体网络,并对认知过程和情绪调节有重要贡献。在这里,我们发现成年小鼠的干细胞产生新神经元的过程伴随着线粒体质量、分布和形状的广泛变化。此外,运动——一种强烈影响成年海马体神经发生的因素——加速了神经元的成熟,并导致线粒体含量的显著增加和线粒体在树突段的存在。线粒体分裂因子 dynamin-related protein 1(Drp1)的活性遗传抑制在基础和运动条件下抑制神经发生。相反,增强 Drp1 的活性进一步促进了运动诱导的神经元成熟加速。总的来说,这些结果表明成年海马体神经发生需要适应线粒体区室,并表明线粒体是增强神经发生依赖性海马体可塑性的靶点。