Donovan Meghan L, Chun Eileen K, Liu Yan, Wang Zuoxin
Program in Neuroscience, Department of Psychology, Florida State University, Tallahassee, FL, United States.
Rocky Mountain Mental Illness Research Education and Clinical Center, Rocky Mountain Regional VA Medical Center, Aurora, CO, United States.
Front Behav Neurosci. 2022 Jan 17;15:802569. doi: 10.3389/fnbeh.2021.802569. eCollection 2021.
The socially monogamous prairie vole () offers a unique opportunity to examine the impacts of adolescent social isolation on the brain, immune system, and behavior. In the current study, male and female prairie voles were randomly assigned to be housed alone or with a same-sex cagemate after weaning (i.e., on postnatal day 21-22) for a 6-week period. Thereafter, subjects were tested for anxiety-like and depressive-like behaviors using the elevated plus maze (EPM) and Forced Swim Test (FST), respectively. Blood was collected to measure peripheral cytokine levels, and brain tissue was processed for microglial density in various brain regions, including the Nucleus Accumbens (NAcc), Medial Amygdala (MeA), Central Amygdala (CeA), Bed Nucleus of the Stria Terminalis (BNST), and Paraventricular Nucleus of the Hypothalamus (PVN). Sex differences were found in EPM and FST behaviors, where male voles had significantly lower total arm entries in the EPM as well as lower latency to immobility in the FST compared to females. A sex by treatment effect was found in peripheral IL-1β levels, where isolated males had a lower level of IL-1β compared to cohoused females. Post-weaning social isolation also altered microglial density in a brain region-specific manner. Isolated voles had higher microglial density in the NAcc, MeA, and CeA, but lower microglial density in the dorsal BNST. Cohoused male voles also had higher microglial density in the PVN compared to cohoused females. Taken together, these data suggest that post-weaning social housing environments can alter peripheral and central immune systems in prairie voles, highlighting a potential role for the immune system in shaping isolation-induced alterations to the brain and behavior.
社会性一夫一妻制的草原田鼠为研究青少年社会隔离对大脑、免疫系统和行为的影响提供了独特的机会。在当前的研究中,雄性和雌性草原田鼠在断奶后(即出生后第21 - 22天)被随机分配单独饲养或与同性笼伴一起饲养6周。此后,分别使用高架十字迷宫(EPM)和强迫游泳试验(FST)对实验对象进行焦虑样和抑郁样行为测试。采集血液以测量外周细胞因子水平,并对脑组织进行处理,以检测包括伏隔核(NAcc)、内侧杏仁核(MeA)、中央杏仁核(CeA)、终纹床核(BNST)和下丘脑室旁核(PVN)在内的各个脑区的小胶质细胞密度。在EPM和FST行为中发现了性别差异,与雌性相比,雄性田鼠在EPM中的总臂进入次数显著更低,在FST中的不动潜伏期也更低。在外周白细胞介素-1β(IL-1β)水平上发现了性别×处理效应,与群居雌性相比,隔离雄性的IL-1β水平更低。断奶后的社会隔离也以脑区特异性方式改变了小胶质细胞密度。隔离的田鼠在NAcc、MeA和CeA中的小胶质细胞密度较高,但在背侧BNST中的小胶质细胞密度较低。与群居雌性相比,群居雄性田鼠在PVN中的小胶质细胞密度也较高。综上所述,这些数据表明断奶后的社会饲养环境可以改变草原田鼠的外周和中枢免疫系统,突出了免疫系统在塑造隔离诱导的大脑和行为改变中的潜在作用。