Department of Behavioural and Molecular Neurobiology, University of Regensburg, Germany.
Hippocampus. 2013 Jun;23(6):476-87. doi: 10.1002/hipo.22107. Epub 2013 Mar 18.
Sex differences in basal as well as in stress-induced hippocampal neurogenesis processes have been reported in the literature. However, studies directly comparing sex differences on multiple neurogenesis processes under such conditions are lacking to date. Therefore, the aim of the present study was to directly compare cell proliferation and survival, neuronal and astroglial differentiation as well as stem cells quiescence in male and female Wistar rats under both basal and chronic stress conditions (12 days of 2 h restraint stress (RS)). In addition, corticosterone (CORT) levels and spatial working memory were assessed. Under baseline conditions, only the number of immature neurons within the hippocampal dentate gyrus was higher in males compared with females. In contrast, chronic stress resulted in a number of sex-specific alterations. Thus, stress exposure reduced cell proliferation in males with a concurrent increase in stem cell quiescence, while it did not alter either parameter in females but decreased cell survival. Analysis of astroglial and neuronal differentiation patterns revealed that chronic stress specifically diminished the number of mature neurons in females, with no effect in males. Despite the observed sex differences in adult hippocampal neurogenesis, spatial working memory was not altered by stress exposure in either sex. While basal CORT levels were higher, chronic stress exposure did not affect this parameter in either sex across the initial stress period. This study presents the first direct and detailed evaluation of sex-dependent and chronic stress-induced changes in adult hippocampal neurogenesis not only showing changes in cell proliferation and survival, but moreover immature neuron production, differentiation patterns, stem cell quiescence and therefore contributes to a better understanding of sex differences in neurogenesis processes.
已有文献报道，在基础状态以及应激诱导的海马神经发生过程中存在性别差异。然而，目前缺乏在这种条件下直接比较多种神经发生过程性别差异的研究。因此，本研究的目的是直接比较雄性和雌性 Wistar 大鼠在基础和慢性应激条件下（12 天 2 小时束缚应激（RS））的细胞增殖和存活、神经元和星形胶质细胞分化以及干细胞静止状态。此外，还评估了皮质酮（CORT）水平和空间工作记忆。在基础状态下，只有雄性海马齿状回内的未成熟神经元数量高于雌性。相比之下，慢性应激导致了一系列特定于性别的改变。因此，应激暴露减少了雄性的细胞增殖，同时增加了干细胞静止，而在雌性中没有改变这两个参数，但减少了细胞存活。对星形胶质细胞和神经元分化模式的分析表明，慢性应激特异性地减少了雌性成熟神经元的数量，而对雄性没有影响。尽管在成年海马神经发生中观察到性别差异，但应激暴露在两性中均未改变空间工作记忆。虽然基础 CORT 水平较高，但在初始应激期间，慢性应激暴露在两性中均未影响该参数。本研究首次直接和详细评估了成年海马神经发生中的性别依赖性和慢性应激诱导的变化，不仅显示了细胞增殖和存活的变化，而且显示了未成熟神经元的产生、分化模式、干细胞静止状态，因此有助于更好地理解神经发生过程中的性别差异。
