Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.
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DOI:
10.1016/j.bbr.2014.12.051
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发表时间:
2015-04-01
影响因子:
2.7
通讯作者:
Conrad, Cheryl D.
Conrad, Cheryl D.
中科院分区:
心理学3区
文献类型:
--
作者:
Ortiz, J. Bryce;Taylor, Sara B.;Hoffman, Ann N.;Campbell, Alyssa N.;Lucas, Louis R.;Conrad, Cheryl D.

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慢性束缚应激以性别依赖性方式改变海马依赖性空间学习和记忆,损害雄性大鼠的空间表现,而使雌性大鼠的空间表现保持完整或促进。此外,这些由压力引起的空间记忆缺陷在男性压力后恢复后得到改善。目前的研究检验了以不可预测的方式实施的约束是否会消除这些性别差异并影响压力后时期的空间能力和边缘谷氨酸脱羧酶(GAD65)表达。雄性 (n=30) 和雌性 (n=30) 成年 Sprague-Dawley 大鼠被分配至非应激对照 (Con)、慢性应激 (Str-Imm) 或给予应激后恢复期的慢性应激 (Str-Rec)。使用每日不重复的物理环境、持续时间和一天中的时间组合,对应激大鼠进行 21 天的出乎意料的限制。然后,所有大鼠在桡臂水迷宫 (RAWM) 上进行为期两天的测试,并在第三天进行一次保留试验,30 分钟后取出大脑以评估 GAD65 mRNA。在 Str-Imm 雄性中,缺陷发生在 RAWM 获取的第一天,这种损伤在 Str-Rec 组中并不明显。相比之下,女性在慢性压力或压力后恢复后没有表现出显着的结果。在男性中,杏仁核 GAD65 表达与第 1 天的 RAWM 表现呈负相关。在女性中,海马 CA1 GAD65 与第 1 天的 RAWM 表现呈正相关。这些结果表明,GABA 能功能可能导致慢性应激后观察到的性别差异。此外,不可预测的限制和恢复期未能消除空间学习和记忆的性别差异。
Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for two days and given one retention trial on the third day, with brains removed 30 minutes later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory.
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