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衰老损害海马体依赖的识别记忆和长时程增强,并阻止相关的兰尼碱受体上调。

Aging Impairs Hippocampal- Dependent Recognition Memory and LTP and Prevents the Associated RyR Up-regulation.

作者信息

Arias-Cavieres Alejandra, Adasme Tatiana, Sánchez Gina, Muñoz Pablo, Hidalgo Cecilia

机构信息

Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de ChileSantiago, Chile.

Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O'HigginsSantiago, Chile.

出版信息

Front Aging Neurosci. 2017 Apr 25;9:111. doi: 10.3389/fnagi.2017.00111. eCollection 2017.

DOI:10.3389/fnagi.2017.00111
PMID:28484388
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5402473/
Abstract

Recognition memory comprises recollection judgment and familiarity, two different processes that engage the hippocampus and the perirhinal cortex, respectively. Previous studies have shown that aged rodents display defective recognition memory and alterations in hippocampal synaptic plasticity. We report here that young rats efficiently performed at short-term (5 min) and long-term (24 h) hippocampus-associated object-location tasks and perirhinal cortex-related novel-object recognition tasks. In contrast, aged rats successfully performed the object-location and the novel-object recognition tasks only at short-term. In addition, aged rats displayed defective long-term potentiation (LTP) and enhanced long-term depression (LTD). Successful long-term performance of object-location but not of novel-object recognition tasks increased the protein levels of ryanodine receptor types-2/3 (RyR2/RyR3) and of IPR1 in young rat hippocampus. Likewise, sustained LTP induction (1 h) significantly increased RyR2, RyR3 and IPR1 protein levels in hippocampal slices from young rats. In contrast, LTD induction (1 h) did not modify the levels of these three proteins. Naïve (untrained) aged rats displayed higher RyR2/RyR3 hippocampal protein levels but similar IPR1 protein content relative to young rats; these levels did not change following exposure to either memory recognition task or after LTP or LTD induction. The perirhinal cortex from young or aged rats did not display changes in the protein contents of RyR2, RyR3, and IPR1 after exposure at long-term (24 h) to the object-location or the novel-object recognition tasks. Naïve aged rats displayed higher RyR2 channel oxidation levels in the hippocampus compared to naïve young rats. The RyR2/RyR3 up-regulation and the increased RyR2 oxidation levels exhibited by aged rat hippocampus are likely to generate anomalous calcium signals, which may contribute to the well-known impairments in hippocampal LTP and spatial memory that take place during aging.

摘要

认知记忆包括回忆判断和熟悉感,这是两个分别涉及海马体和内嗅皮质的不同过程。先前的研究表明,老年啮齿动物表现出认知记忆缺陷以及海马体突触可塑性的改变。我们在此报告,年轻大鼠在短期(5分钟)和长期(24小时)与海马体相关的物体定位任务以及与内嗅皮质相关的新物体识别任务中表现良好。相比之下,老年大鼠仅在短期成功完成了物体定位和新物体识别任务。此外,老年大鼠表现出长时程增强(LTP)缺陷和长时程抑制(LTD)增强。物体定位任务的长期成功表现而非新物体识别任务的长期成功表现增加了年轻大鼠海马体中2型/3型兰尼碱受体(RyR2/RyR3)和肌醇1,4,5-三磷酸受体1(IPR1)的蛋白质水平。同样,持续的LTP诱导(1小时)显著增加了年轻大鼠海马体切片中RyR2、RyR3和IPR1的蛋白质水平。相比之下,LTD诱导(1小时)并未改变这三种蛋白质的水平。未经训练的老年大鼠相对于年轻大鼠,海马体中RyR2/RyR3蛋白质水平较高,但IPR1蛋白质含量相似;在经历记忆识别任务或LTP或LTD诱导后,这些水平并未改变。在长期(24小时)暴露于物体定位或新物体识别任务后,年轻或老年大鼠的内嗅皮质中RyR2、RyR3和IPR1的蛋白质含量没有变化。未经训练的老年大鼠与未经训练的年轻大鼠相比,海马体中RyR2通道氧化水平更高。老年大鼠海马体中RyR2/RyR3上调和RyR2氧化水平增加可能会产生异常的钙信号,这可能导致衰老过程中发生的海马体LTP和空间记忆的众所周知的损伤。

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