title: Voluntary exercise attenuates LPS-induced reductions in neurogenesis and increases microglia expression of a proneurogenic phenotype in aged mice.
abstract: 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.
authors.affiliation: Department of Psychology, University of North Carolina Wilmington, 601 S. College Road, Wilmington, NC, 28403-5612, USA. aml8440@uncw.edu.
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Littlefield
authors.affiliation: Department of Psychology, University of North Carolina Wilmington, 601 S. College Road, Wilmington, NC, 28403-5612, USA. ses8535@uncw.edu.
authors.forename: Sharay E
authors.initials: SE
authors.lastname: Setti
authors.affiliation: Department of Biology, University of North Carolina Wilmington, 601 S. College Road, Wilmington, NC, 28403-5612, USA. priesterc@uncw.edu.
authors.forename: Carolina
authors.initials: C
authors.lastname: Priester
authors.affiliation: Department of Psychology, University of North Carolina Wilmington, 601 S. College Road, Wilmington, NC, 28403-5612, USA. kohmanr@uncw.edu.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Kohman
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D023421:Models, Animal; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D055495:Neurogenesis / Q000187:drug effects; D010641:Phenotype; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012420:Running / Q000502:physiology; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008070:Lipopolysaccharides