Aging and infection reduce expression of specific brain-derived neurotrophic factor mRNAs in hippocampus

Neurobiol Aging. 2012 Apr;33(4):832.e1-14. doi: 10.1016/j.neurobiolaging.2011.07.015. Epub 2011 Sep 9.

Abstract

Aging increases the likelihood of cognitive decline after negative life events such as infection or injury. We have modeled this increased vulnerability in aged (24-month-old), but otherwise unimpaired F344xBN rats. In these animals, but not in younger (3-month-old) counterparts, a single intraperitoneal injection of E. coli leads to specific deficits in long-term memory and long-lasting synaptic plasticity in hippocampal area CA1-processes strongly dependent on brain-derived neurotrophic factor (BDNF). Here we have investigated the effects of age and infection on basal and fear-conditioning-stimulated expression of Bdnf in hippocampus. We performed in situ hybridization with 6 probes recognizing: total (pan-)BDNF mRNA, the 4 predominant 5' exon-specific transcripts (I, II, IV, and VI), and BDNF mRNAs with a long 3' untranslated region (3' UTR). In CA1, aging reduced basal levels and fear-conditioning-induced expression of total BDNF mRNA, exon IV-specific transcripts, and transcripts with long 3' UTRs; effects of infection were similar and sometimes compounded the effects of aging. In CA3, aging reduced all of the transcripts to some degree; infection had no effect. Effects in dentate were minimal. Northern blot analysis confirmed an aging-associated loss of total BDNF mRNA in areas CA1 and CA3, and revealed a parallel, preferential loss of BDNF mRNA transcripts with long 3' UTRs.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / genetics
  • Age Factors
  • Aging / pathology*
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Disease Models, Animal
  • Escherichia coli Infections / pathology*
  • Exons / genetics
  • Fear / psychology
  • Gene Expression Regulation / physiology*
  • Hippocampus / metabolism*
  • Male
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Inbred F344

Substances

  • 3' Untranslated Regions
  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger