Differential effects of duration and age on the consequences of neuroinflammation in the hippocampus

Isabelle Bardou, Holly M. Brothers, Roxanne M. Kaercher, Sarah C. Hopp, Gary L. Wenk

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The current study investigated the hypothesis that the duration of the proinflammatory environment plays a critical role in the brain's response that results in negative consequences on cognition, biochemistry, and pathology. Lipopolysaccharide or artificial cerebrospinal fluid was slowly (250 ηg/h) infused into the fourth ventricle of young (3-month-old), adult (9-month-old), or aged (23-month-old) male F-344 rats for 21 or 56 days. The rats were then tested in the water pool task and endogenous hippocampal levels of pro- and anti-inflammatory proteins and genes and indicators of glutamatergic function were determined. The duration of the lipopolysaccharide infusion, compared with the age of the rat, had the greatest effect on (1) spatial working memory; (2) the density and distribution of activated microglia within the hippocampus; and (3) the cytokine protein and gene expression profiles within the hippocampus. The duration- and age-dependent consequences of neuroinflammation might explain why human adults respond positively to anti-inflammatory therapies and aged humans do not.

Original languageEnglish (US)
Pages (from-to)2293-2301
Number of pages9
JournalNeurobiology of Aging
Volume34
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Aging
  • Cytokines
  • Lipopolysaccharide
  • Migroglia
  • PCR
  • Rats
  • Water pool task

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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