School of Biomedical Sciences and Pharmacy, Centre for Brain and Mental Health Research, University of Newcastle, New South Wales 2308, Australia.
Cereb Cortex. 2012 Jun;22(6):1442-54. doi: 10.1093/cercor/bhr229. Epub 2011 Aug 30.
Psychological stress contributes to the development of clinical depression. This has prompted many preclinical studies to investigate the neurobiology of this relationship, however, the effects of stress on glia remain unclear. In this study, we wished to determine, first, how exposure to chronic psychological stress affects microglial activity within the prefrontal cortex (PFC) and, second, whether the observed changes were meaningfully related to corresponding changes in local neuronal activity and PFC-regulated behavior. Therefore, we examined markers of microglial activation, antigen presentation, apoptosis, and persistent neuronal activation within the PFC after exposure to repeated restraint stress. We also examined the effect of stress on spatial working memory, a PFC-dependent function. Finally, we tested the ability of a microglial activation inhibitor (minocycline) to alter the impact of chronic stress on all of these endpoints. Stressor exposure produced positively correlated increases in microglial and long-term neuronal activation in the PFC but not antigen presentation or apoptosis. As expected, it also impaired spatial working memory. Importantly, minocycline reduced the impact of stress on neuronal activation and working memory, as well as microglial activation. These results suggest a role for microglia in mediating the effects of stress on PFC neuronal function and PFC-regulated behavior.
心理压力会导致临床抑郁症的发展。这促使许多临床前研究调查这种关系的神经生物学，但压力对神经胶质细胞的影响仍不清楚。在这项研究中，我们首先想确定，慢性心理压力暴露如何影响前额叶皮层（PFC）内的小胶质细胞活性，其次，观察到的变化是否与局部神经元活性和 PFC 调节的行为的相应变化有意义相关。因此，我们检查了 PFC 中小胶质细胞激活、抗原呈递、细胞凋亡和持续神经元激活的标志物，这些标志物在重复束缚应激后出现。我们还研究了应激对空间工作记忆（一种与 PFC 相关的功能）的影响。最后，我们测试了小胶质细胞激活抑制剂（米诺环素）改变慢性应激对所有这些终点的影响的能力。应激源暴露导致 PFC 中小胶质细胞和长期神经元激活呈正相关增加，但不包括抗原呈递或细胞凋亡。正如预期的那样，它还损害了空间工作记忆。重要的是，米诺环素降低了应激对神经元激活和工作记忆以及小胶质细胞激活的影响。这些结果表明小胶质细胞在介导应激对 PFC 神经元功能和 PFC 调节行为的影响中起作用。
