Voluntary exercise attenuates LPS-induced reductions in neurogenesis and increases microglia expression of a proneurogenic phenotype in aged mice.
Voluntary exercise attenuates LPS-induced reductions in neurogenesis and increases microglia expression of a proneurogenic phenotype in aged mice.
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DOI：
10.1186/s12974-015-0362-0
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发表时间：
2015-07-30
影响因子：
9.3
通讯作者：
Kohman RA
中科院分区：
文献类型：
--
作者：
Littlefield AM;Setti SE;Priester C;Kohman RA
小胶质细胞可以获得介导其炎症和神经保护作用的各种活化表型。老化导致小胶质细胞部分活化，从而形成炎症表型。因此，老年动物在免疫攻击后表现出延长的神经炎症反应。目前尚不清楚这种持续的神经炎症是否会导致海马神经发生的更大程度的减少。运动已被证明改变了老年动物的小胶质细胞活化，但这些变化的性质尚未完全阐明。本研究评估了老年小鼠在脂多糖（LPS）急性免疫攻击后海马神经发生是否表现出增强的减少。此外，我们评估了自愿轮运行是否保护免受LPS的影响。将成年（4个月）和老年（22个月）雄性C57 BL 6/J小鼠单独圈养（有或没有转轮），共9周。5周后，小鼠接受单次腹膜内LPS或盐水注射，并每天注射四次溴脱氧尿苷（BrdU）以标记分裂细胞。4周后收集组织并进行免疫组织化学以测量新细胞存活、新神经元数目和小胶质细胞活化。数据显示，LPS减少了老年小鼠而不是成年小鼠的新神经元数量。这些LPS诱导的老年小鼠神经发生减少可通过轮跑来预防。此外，运动增加了老年人小胶质细胞与脑源性神经营养因子（BDNF）共标记的比例。总之，研究结果表明，自主转轮运动可能促进神经保护性小胶质细胞表型，并防止老年脑中炎症诱导海马神经发生减少。
Microglia can acquire various phenotypes of activation that mediate their inflammatory and neuroprotective effects. Aging causes microglia to become partially activated towards an inflammatory phenotype. As a result, aged animals display a prolonged neuroinflammatory response following an immune challenge. Currently unknown is whether this persistent neuroinflammation leads to greater reductions in hippocampal neurogenesis. Exercise has been shown to alter microglia activation in aged animals, but the nature of these changes has yet to be fully elucidated. The present study assessed whether aged mice show enhanced reductions in hippocampal neurogenesis following an acute immune challenge with lipopolysaccharide (LPS). Further, we assessed whether voluntary wheel running protects against the effects of LPS. Adult (4 months) and aged (22 months) male C57BL6/J mice were individually housed with or without a running wheel for a total of 9 weeks. After 5 weeks, mice received a single intraperitoneal LPS or saline injection in combination with four daily injections of bromodeoxyuridine (BrdU) to label dividing cells. Tissue was collected 4 weeks later and immunohistochemistry was conducted to measure new cell survival, new neuron numbers, and microglia activation. Data show that LPS reduced the number of new neurons in aged, but not adult, mice. These LPS-induced reductions in neurogenesis in the aged mice were prevented by wheel running. Further, exercise increased the proportion of microglia co-labeled with brain-derived neurotrophic factor (BDNF) in the aged. Collectively, findings indicate that voluntary wheel running may promote a neuroprotective microglia phenotype and protect against inflammation-induced reductions in hippocampal neurogenesis in the aged brain.