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首页> 外文期刊>The European Journal of Neuroscience >Hippocampal brain-derived neurotrophic factor mediates recovery from chronic stress-induced spatial reference memory deficits
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Hippocampal brain-derived neurotrophic factor mediates recovery from chronic stress-induced spatial reference memory deficits

机译：海马脑源性神经营养因子介导慢性应激诱发的空间参考记忆缺陷的恢复

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摘要

Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain-derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the dorsal hippocampal cornu ammonis (CA)3 region with an adeno-associated viral vector containing the sequence for a short hairpin RNA (shRNA) directed against BDNF or a scrambled sequence (Scr). Rats were then chronically restrained (wire mesh, 6h/day for 21days) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trials. Rats in the Str-Imm group, regardless of adeno-associated viral contents, committed more errors in the spatial reference memory domain on the single retention trial during day 3 than did the non-stressed controls. Importantly, the typical improvement in spatial memory following the recovery from chronic stress was blocked with the shRNA against BDNF, as Str-Rec-shRNA performed worse on the RAWM compared with the non-stressed controls or Str-Rec-Scr. The stress effects were specific for the reference memory domain, but knockdown of hippocampal BDNF in unstressed controls briefly disrupted spatial working memory as measured by repeated entry errors on day 2 of training. These results demonstrated that hippocampal BDNF was necessary for the recovery from stress-induced hippocampal-dependent spatial memory deficits in the reference memory domain.
机译：慢性束缚应激会损害海马介导的空间学习和记忆，在应激后恢复期后会改善。在这里，我们研究了脑源性神经营养因子（BDNF）（一种对海马功能重要的蛋白）是否会改变从慢性应激引起的空间记忆障碍中恢复的能力。将成年雄性Sprague-Dawley大鼠通过腺相关病毒载体注入到海马背侧角膜（CA）3区域，该病毒载体含有针对BDNF的短发夹RNA（shRNA）序列或加扰序列（Scr）。然后将大鼠长期约束（金属丝网，每天6h /天，持续21天），并在应激源停止后（Str-Imm）或在应激21天后立即使用a臂水迷宫（RAWM）评估其空间学习和记忆能力恢复期（Str-Rec）。所有组都相似地学习了RAWM任务，但是在记忆保留试验上有所不同。与非应激对照组相比，Str-Imm组的大鼠，无论与腺相关的病毒含量如何，在第3天的单次保留试验中，在空间参考记忆域中的错误就更多。重要的是，从慢性应激恢复后，空间记忆的典型改善被针对BDNF的shRNA阻断，因为与非应激对照组或Str-Rec-Scr相比，Str-Rec-shRNA在RAWM上的表现更差。应激效应是特定于参考记忆域的，但是在无压力对照中海马BDNF的敲低会短暂破坏空间工作记忆，这是通过训练第2天的重复输入错误来衡量的。这些结果表明，海马BDNF对于从参考记忆域中的应激诱导的海马依赖性空间记忆缺陷中恢复是必需的。

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