Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan.
Department of Physiology, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan.
Int J Mol Sci. 2023 Jan 19;24(3):1983. doi: 10.3390/ijms24031983.
An escapable (ES)/inescapable stress (IS) paradigm was used to study whether behavioral control and repeated footshock stressors may affect adult neurogenesis and related cognitive function. Male stressed mice having behavioral control (ES) had a short-term escalation in dorsal dentate gyrus (DG) neurogenesis, while similarly stressed mice having no such control had unaltered neurogenesis as compared to control mice receiving no stressors. Paradoxically, ES and IS mice had comparable stress-induced corticosterone elevations throughout the stress regimen. Appetitive operant conditioning and forced running procedures were used to model learning and exercise effects in this escapable/inescapable paradigm. Further, conditioning and running procedures did not seem to affect the mice's corticosterone or short-term neurogenesis. ES and IS mice did not show noticeable long-term changes in their dorsal DG neurogenesis, gliogenesis, local neuronal density, apoptosis, autophagic flux, or heterotypic stress responses. ES mice were found to have a greater number of previously labeled and functionally integrated DG neurons as compared to IS and control mice 6 weeks after the conclusion of the stressor regimen. Likewise, ES mice outperformed IS and non-stressed control mice for the first two, but not the remaining two, trials in the object location task. Compared to non-stressed controls, temozolomide-treated ES and IS mice having a lower number of dorsal DG 6-week-old neurons display poor performance in their object location working memory. These results, taken together, prompt us to conclude that repeated stressors, albeit their corticosterone secretion-stimulating effect, do not necessary affect adult dorsal DG neurogenesis. Moreover, stressed animals having behavioral control may display adult neurogenesis escalation in the dorsal DG. Furthermore, the number of 6-week-old and functionally-integrated neurons in the dorsal DG seems to confer the quality of spatial location working memory. Finally, these 6-week-old, adult-born neurons seem to contribute spatial location memory in a use-dependent manner.
一种可逃避（ES）/不可逃避应激（IS）范式被用于研究行为控制和重复足底电击应激源是否会影响成年神经发生和相关认知功能。具有行为控制（ES）的雄性应激小鼠的背齿状回（DG）神经发生出现短期急剧增加，而同样受到应激但没有这种控制的小鼠的神经发生与未接受应激源的对照小鼠没有变化。矛盾的是，ES 和 IS 小鼠在整个应激过程中具有可比的应激诱导皮质酮升高。食欲操作性条件反射和强制跑步程序用于在这种可逃避/不可逃避范式中模拟学习和运动效应。此外，条件反射和跑步程序似乎不会影响小鼠的皮质酮或短期神经发生。ES 和 IS 小鼠在其背侧 DG 神经发生、神经胶质发生、局部神经元密度、细胞凋亡、自噬通量或异质应激反应中没有显示出明显的长期变化。与 IS 和对照小鼠相比，ES 小鼠在应激方案结束后 6 周时具有更多先前标记和功能整合的 DG 神经元。同样，与 IS 和非应激对照小鼠相比，ES 小鼠在前两次（但不是后两次）物体位置任务中表现更好。与非应激对照相比，接受替莫唑胺治疗的 ES 和 IS 小鼠具有较少的背侧 DG 6 周龄神经元，在物体位置工作记忆方面表现不佳。这些结果表明，尽管应激源会刺激皮质酮的分泌，但它们不一定会影响成年背侧 DG 的神经发生。此外，具有行为控制的应激动物可能会在背侧 DG 中显示出成年神经发生的增加。此外，背侧 DG 中 6 周龄和功能整合神经元的数量似乎赋予了空间位置工作记忆的质量。最后，这些 6 周龄的成年新生神经元似乎以依赖使用的方式有助于空间位置记忆。
