Voluntary exercise attenuates LPS-induced reductions in neurogenesis and increases microglia expression of a proneurogenic phenotype in aged mice

Journal of Neuroinflammation

Rachel A. Kohman²  Carolina Priester¹  Sharay E. Setti²  Alyssa M. Littlefield² 

[1] Department of Biology, University of North Carolina Wilmington, 601 S. College Road, Wilmington 28403-5612, NC, USA;Department of Psychology, University of North Carolina Wilmington, 601 S. College Road, Wilmington 28403-5612, NC, USA

关键词: Hippocampus;    Spatial learning;    Lipopolysaccharide;    Wheel running;    BDNF;   

Others  :  1221907
DOI  :  10.1186/s12974-015-0362-0

 received in 2015-02-16, accepted in 2015-07-17,  发布年份 2015

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2015 Littlefield et al.

【 图 表 】

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