Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.
Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.
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DOI：
10.1371/journal.pone.0002170
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发表时间：
2008-05-14
期刊：
影响因子：
3.7
通讯作者：
Maccari S
中科院分区：
文献类型：
--
作者：
Zuena AR;Mairesse J;Casolini P;Cinque C;Alemà GS;Morley-Fletcher S;Chiodi V;Spagnoli LG;Gradini R;Catalani A;Nicoletti F;Maccari S
胎儿期束缚应激(Prs)是一种有效的早期应激模型，可导致永久性的行为和神经生物学结果。尽管30多年来人们一直在假想性分裂的影响，但在这么长的一段时间里，很少有研究直接解决这个问题。我们的团队已经发现，在怀孕的最后10天，PR(在怀孕的最后10天里每天给母亲3次压力)对焦虑、空间学习和一系列神经生物学参数的影响存在显著的性别差异，这些参数通常与海马体依赖行为有关。成年雄性大鼠(“PRS大鼠”)表现出在高架+迷宫(EPM)中焦虑样行为增加，齿状回新生细胞存活率降低，腹侧海马区mGlu1/5代谢型谷氨酸受体活性降低，海马区脑源性神经营养因子(BDNF)和BDNF原水平增加。相比之下，雌性PRS大鼠在EPM中的焦虑程度降低，在Morris水迷宫中的学习能力得到改善，腹侧和背侧海马区mGlu1/5受体的活性增加，而海马神经发生和BDNF水平没有变化。PRS动物的神经发生、BDNF水平和mGlu受体功能的变化方向与行为变化不一致，提示PRS干扰了这些特殊参数的相互依赖及其与海马区依赖行为的关系。我们的数据表明，早期环境挑战引起的海马神经可塑性的表观遗传变化是严重的性别依赖，男性和女性的行为结果可能会有所不同。
Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy) on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS (“PRS rats”) showed increased anxiety-like behavior in the elevated plus maze (EPM), a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females.
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影响因子：
9.8
作者：
Dupret D;Fabre A;Döbrössy MD;Panatier A;Rodríguez JJ;Lamarque S;Lemaire V;Oliet SH;Piazza PV;Abrous DN
通讯作者：
Abrous DN
影响因子：
4.2
作者：
Darnaudéry, M;Perez-Martin, M;Garcia-Segura, LM
通讯作者：
Garcia-Segura, LM
影响因子：
4.8
作者：
Bowman, RE;MacLusky, NJ;Luine, VN
通讯作者：
Luine, VN
影响因子：
3.6
作者：
Brodkin, J;Busse, C;Varney, MA
通讯作者：
Varney, MA
影响因子：
5.3
作者：
Earnheart, John C.;Schweizer, Claude;Luscher, Bernhard
通讯作者：
Luscher, Bernhard