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

• Published in: Neurobiology of aging Vol. 33; no. 4; pp. 832.e1 - 832.e14
• Main Authors: Chapman, Timothy R, Barrientos, Ruth M, Ahrendsen, Jared T, Hoover, Jennifer M, Maier, Steven F, Patterson, Susan L
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2012
• Subjects: 3' Untranslated Regions - genetics; Age Factors; Aging; Aging - pathology; Animals; BDNF mRNA; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cytokines; Dendrites; Disease Models, Animal; Escherichia coli; Escherichia coli Infections - pathology; Exons; Exons - genetics; Fear - psychology; Gene Expression Regulation - physiology; Hippocampus; Hippocampus - metabolism; IL-1β; Infection; Inflammation; Interleukin-1; Internal Medicine; Learning; Lipopolysaccharide; Long 3′ UTR; LTP; Male; Memory; Neurology; Rats; Rats, Inbred F344; RNA, Messenger - metabolism; Interleukin-1; Cytokines; Exons; Memory; LTP; Inflammation; IL-1β; Learning; Infection; Aging; Lipopolysaccharide; Long 3′ UTR; Dendrites; BDNF mRNA; Hippocampus; Transcripts
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2011.07.015

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.