Department of Psychology and Neuroscience and The Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
Neurobiol Aging. 2012 Apr;33(4):832.e1-14. doi: 10.1016/j.neurobiolaging.2011.07.015. Epub 2011 Sep 9.
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.
衰老增加了负面生活事件（如感染或受伤）后认知能力下降的可能性。我们已经对年龄较大（24 个月大）但无其他损伤的 F344xBN 大鼠进行了这种易感性增加的建模。在这些动物中，但在年轻（3 个月大）的对应物中，单次腹腔注射大肠杆菌会导致海马 CA1 区的长期记忆和长期突触可塑性出现特定缺陷，这些过程强烈依赖于脑源性神经营养因子（BDNF）。在这里，我们研究了年龄和感染对海马中 Bdnf 基础表达和恐惧条件刺激表达的影响。我们使用 6 个探针进行了原位杂交，这些探针可识别：总（泛）BDNF mRNA、4 个主要的 5' 外显子特异性转录本（I、II、IV 和 VI）以及具有长 3' 非翻译区（3'UTR）的 BDNF mRNA。在 CA1 区，衰老降低了总 BDNF mRNA、外显子 IV 特异性转录本和具有长 3'UTR 的转录本的基础水平和恐惧条件刺激诱导的表达；感染的影响相似，有时甚至加剧了衰老的影响。在 CA3 区，衰老在某种程度上降低了所有的转录本；感染没有影响。齿状回的影响最小。Northern blot 分析证实了 CA1 和 CA3 区总 BDNF mRNA 与年龄相关的丢失，并揭示了具有长 3'UTR 的 BDNF mRNA 转录本的平行优先丢失。
