RESUMEN
Many people experience traumatic events during their lives, but not all of them develop severe mental pathologies, characterized by high levels of anxiety that persists for more than a month after psychological trauma, such as posttraumatic stress disorder (PTSD). We used a single prolonged stress protocol in order to model PTSD in long-inbred C57BL/6 and wild-derived (house) female mice. The susceptibility of mice to single prolonged stress was assessed by behavior phenotyping in the Open Field and Elevated Plus Maze, the level of neuroinflammation in the hippocampus was estimated by real-time PCR to TNFα, IL-1ß, IL-6, IL-10, Iba1 and GFAP, as well as immunohistochemical analysis of microglial morphology and mean fluorescence intensity for GFAP+ cells. The level of neurogenesis was analyzed by real-time PCR to Ki67, Sox2 and DCX as well as immunohistochemistry to Ki67. We showed that long-inbread C57BL/6 mice are more susceptible to a single prolonged stress protocol compared to wild-derived (house) mice. Stressed C57BL/6 mice demonstrated elevated expression levels of proinflammatory cytokines TNFα, IL-1ß, and IL-6 in the hippocampus, while in house mice no differences in cytokine expression were detected. Expression levels of Iba1 in the hippocampus did not change significantly after single prolonged stress, however GFAP expression increased substantially in stressed C57BL/6 mice. The number of Iba+ cells in the dentate gyrus also did not change after stress, but the morphology of Iba+ microglia in C57BL/6 animals allowed us to suggest that it was activated; house mice also had significantly more microglia than C57BL/6 animals. We suppose that decreased microglia levels in the hippocampus of C57BL/6 compared to house mice might be one of the reasons for their sensitivity to a single prolonged stress. Single prolonged stress reduced the number of Ki67+ proliferating cells in the dentate gyrus of the hippocampus but only in C57BL/6 mice, not in house mice, with the majority of cells detected in the dorsal (septal) hippocampus in both. The increase in the expression level of DCX might be a compensatory reaction to stress; however, it does not necessarily mean that these immature neurons will be functionally integrated, and this issue needs to be investigated further.
RESUMEN
An enriched environment stimulates adult hippocampal plasticity, but the exact cellular and molecular mechanisms are complex, and thus a matter of debate. We studied the behavior and hippocampal neurogenesis in adult male and female Wistar rats that were housed in an enriched environment (EE) for two months. Both EE males and females performed better than control animals in a Barnes maze, meaning that EE enhances spatial memory. However, the expression levels of neurogenesis markers KI67, DCX, Nestin, and Syn1 increased only in EE females, while in EE males only KI67 and BDNF were higher than in the corresponding control. The number of DCX+ neurons on brain slices increased in the dentate gyrus of EE females only, i.e., the level of adult hippocampal neurogenesis was increased in female but not in male rats. The level of anti-inflammatory IL-10 and signaling pathway components was upregulated in EE females. Of 84 miRNAs tested, in the hippocampi of EE female rats we detected upregulation in the expression levels of 12 miRNAs related to neuronal differentiation and morphogenesis, while in EE males four miRNAs were upregulated and involved in the regulation of cell proliferation/differentiation, and one was downregulated and associated with the stimulation of proliferation. Taken altogether, our results point to sex-specific differences in adult hippocampal plasticity, IL-10 expression, and miRNA profiles induced by an enriched environment.