title: Aging and infection reduce expression of specific brain-derived neurotrophic factor mRNAs in hippocampus.
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.
authors: Department of Psychology and Neuroscience and The Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
authors: Timothy R
authors: TR
authors: Chapman
authors: Ruth M
authors: RM
authors: Barrientos
authors: Jared T
authors: JT
authors: Ahrendsen
authors: Jennifer M
authors: JM
authors: Hoover
authors: Steven F
authors: SF
authors: Maier
authors: Susan L
authors: SL
authors: Patterson
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000367:Age Factors; D000375:Aging / Q000473:pathology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000473:pathology*; D005091:Exons / Q000235:genetics; D005239:Fear / Q000523:psychology; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D020413:3' Untranslated Regions; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger