Early life stress leads to developmental and sex selective effects on performance in a novel object placement task.
Early life stress leads to developmental and sex selective effects on performance in a novel object placement task.
复制标题
DOI：
10.1016/j.ynstr.2017.04.001
复制
发表时间：
2017-12
影响因子：
5
通讯作者：
Manzano-Nieves G
中科院分区：
文献类型：
--
作者：
Bath KG;Nitenson AS;Lichtman E;Lopez C;Chen W;Gallo M;Goodwill H;Manzano-Nieves G
早期生活护理的中断，包括忽视、极端贫困和创伤，会影响神经发育，增加病理的风险和严重程度。在情感病理方面已经发现了显著的性别差异，女性患焦虑和抑郁障碍的风险更高。然而，早期生活压力（ELS）对认知发展的影响尚未得到很好的表征，特别是在ELS对认知能力发育的性别特异性影响方面。在小鼠中，由于产妇卧床限制而导致的产妇护理碎片化，用于诱导ELS。在不同的早期发展阶段（P21, P28, P38， P50和P75），使用新物体放置（NOP）任务跟踪空间能力的发展。与对照组相比，暴露于ELS的雄性小鼠在所有年龄段的NOP任务中都表现出明显的损伤。在雌性小鼠中，ELS在断奶后立即（P21）和青春期周围（P38）导致NOP表现受损，但这些影响不会持续到成年早期。先前的研究表明，海马神经发生受损可能是ELS男性负面结果的中介。在行为学naïve动物的海马中，随着小鼠年龄的增长，Ki-67（增殖标志物）和双皮质素（dcx -未成熟细胞标志物）的表达显著下降，ELS饲养的小鼠这些标志物的发育下降速度更快。然而，ELS的作用被P28所消除，没有观察到性别的主要影响。这些结果表明，ELS对雄性和雌性小鼠的空间能力的发展都有影响，而且这些影响在雄性小鼠中更为深远和持久。ELS导致小鼠空间记忆能力的性别差异。雌性小鼠表现出在青春期前消退的能力受损。雄性小鼠在生命早期表现出持续的损伤。影响仅限于空间能力，而不是其他任务维度。效果与海马的增殖和分化标志物无关。
Disruptions in early life care, including neglect, extreme poverty, and trauma, influence neural development and increase the risk for and severity of pathology. Significant sex disparities have been identified for affective pathology, with females having an increased risk of developing anxiety and depressive disorder. However, the effects of early life stress (ELS) on cognitive development have not been as well characterized, especially in reference to sex specific impacts of ELS on cognitive abilities over development. In mice, fragmented maternal care resulting from maternal bedding restriction, was used to induce ELS. The development of spatial abilities were tracked using a novel object placement (NOP) task at several different ages across early development (P21, P28, P38, P50, and P75). Male mice exposed to ELS showed significant impairments in the NOP task compared with control reared mice at all ages tested. In female mice, ELS led to impaired NOP performance immediately following weaning (P21) and during peri-adolescence (P38), but these effects did not persist into early adulthood. Prior work has implicated impaired hippocampus neurogenesis as a possible mediator of negative outcomes in ELS males. In the hippocampus of behaviorally naïve animals there was a significant decrease in expression of Ki-67 (proliferative marker) and doublecortin (DCX-immature cell marker) as mice aged, and a more rapid developmental decline in these markers in ELS reared mice. However, the effect of ELS dissipated by P28 and no main effect of sex were observed. Together these results indicate that ELS impacts the development of spatial abilities in both male and female mice and that these effects are more profound and lasting in males. ELS leads to sex differences in spatial memory abilities in mice. Female mice show impaired performance that resolve prior to adolescence. Male mice show persistent impairments across early life. Effects are restricted to spatial abilities and not other task dimensions. Effects are not related to markers of proliferation and differentiation in hippocampus.