PPARγ activation prevents impairments in spatial memory and neurogenesis following transient illness

Brain Behav Immun. 2013 Mar:29:28-38. doi: 10.1016/j.bbi.2012.10.017. Epub 2012 Oct 26.

Abstract

The detrimental effects of illness on cognition are familiar to virtually everyone. Some effects resolve quickly while others may linger after the illness resolves. We found that a transient immune response stimulated by lipopolysaccharide (LPS) compromised hippocampal neurogenesis and impaired hippocampus-dependent spatial memory. The immune event caused an ∼50% reduction in the number of neurons generated during the illness and the onset of the memory impairment was delayed and coincided with the time when neurons generated during the illness would have become functional within the hippocampus. Broad spectrum non-steroidal anti-inflammatory drugs attenuated these effects but selective Cox-2 inhibition was ineffective while PPARγ activation was surprisingly effective at protecting both neurogenesis and memory from the effects of LPS-produced transient illness. These data may highlight novel mechanisms behind chronic inflammatory and neuroinflammatory episodes that are known to compromise hippocampus-dependent forms of learning and memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antimetabolites
  • Bromodeoxyuridine
  • Cell Count
  • Data Interpretation, Statistical
  • Female
  • Hippocampus / physiology
  • Illness Behavior / drug effects
  • Illness Behavior / physiology*
  • Immunohistochemistry
  • Learning / physiology
  • Lipopolysaccharides / pharmacology*
  • Maze Learning / drug effects
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neurogenesis / physiology*
  • PPAR gamma / metabolism*
  • Space Perception / physiology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antimetabolites
  • Lipopolysaccharides
  • PPAR gamma
  • Bromodeoxyuridine