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

NEUROBIOLOGY OF AGING

卷:33

Article

Patterson, Susan L.¹ 

[1] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA

关键词: Aging;    Inflammation;    Interleukin-1;    IL-1 beta;    LTP;    Learning;    Memory;    Hippocampus;    Infection;    BDNF mRNA;    Long 3 ' UTR;    Exons;    Transcripts;    Cytokines;    Lipopolysaccharide;    Dendrites;   

DOI  :  10.1016/j.neurobiolaging.2011.07.015

来源: Elsevier

【 摘 要 】

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. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

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