Zhang Ariel Y, Elias Elias, White Abigail G, Jones Laura G, Hamad Taleen, Manners Melissa T
Department of Biological and Biomedical Sciences, Rowan University, Glassboro, NJ, 08028, USA.
Sci Rep. 2025 Sep 26;15(1):33285. doi: 10.1038/s41598-025-18000-2.
Chronic stress has been associated with an increased inflammatory profile in the brain, linking inflammation to the development of stress-related disorders. Although the detailed mechanism connecting chronic stress to inflammation remains unclear, as primary mediators of the immune response, it has been established that microglia play a role. We further investigated the effect of chronic stress on microglia reactivity by incorporating sex and multiple brain regions as variables in our analysis. We utilized the unpredictable chronic mild stress (UCMS) paradigm and then quantified the number of microglia, process arborization, process length, and the number of processes of microglia in the prefrontal cortex (PFC), nucleus accumbens (NAC), hypothalamus (HYPO), amygdala (AMY), and hippocampal CA1 and CA3. We did not observe a stress-induced change in the number of microglia in each region; however, chronic stress reduced microglia arborization, length, and number of processes in a brain region and sex-specific manner. Independent of stress, microglia exhibited a region-dependent reactive phenotype. Together, chronic stress affects microglia reactivity uniquely based on sex and brain region, while the different reactivity profile of microglia in males and females might underlie the sex-specific mechanism of the diseases.
慢性应激与大脑中炎症水平升高有关，将炎症与应激相关疾病的发展联系起来。尽管将慢性应激与炎症联系起来的详细机制尚不清楚，但作为免疫反应的主要介质，已确定小胶质细胞发挥了作用。我们通过在分析中纳入性别和多个脑区作为变量，进一步研究了慢性应激对小胶质细胞反应性的影响。我们采用不可预测的慢性轻度应激（UCMS）范式，然后量化前额叶皮质（PFC）、伏隔核（NAC）、下丘脑（HYPO）、杏仁核（AMY）以及海马CA1和CA3中小胶质细胞的数量、突起分支、突起长度和突起数量。我们没有观察到应激诱导的各脑区小胶质细胞数量变化；然而，慢性应激以脑区和性别特异性的方式减少了小胶质细胞的分支、长度和突起数量。与应激无关，小胶质细胞表现出区域依赖性的反应表型。总之，慢性应激根据性别和脑区独特地影响小胶质细胞反应性，而雄性和雌性小胶质细胞不同的反应特征可能是疾病性别特异性机制的基础。
