Myers Teneisha, Birmingham Elizabeth A, Rhoads Brigham T, McGrath Anna G, Miles Nylah A, Schuldt Carmen B, Briand Lisa A
Neuroscience Program, Temple University, Philadelphia, PA, United States.
Department of Psychology and Neuroscience, Temple University, Philadelphia, PA, United States.
Front Behav Neurosci. 2024 Aug 29;18:1444596. doi: 10.3389/fnbeh.2024.1444596. eCollection 2024.
Adolescence is a critical period for brain development in humans and stress exposure during this time can have lasting effects on behavior and brain development. Social isolation and loneliness are particularly salient stressors that lead to detrimental mental health outcomes particularly in females, although most of the preclinical work on social isolation has been done in male animals. Our lab has developed a model of post-weaning adolescent social isolation that leads to increased drug reward sensitivity and altered neuronal structure in limbic brain regions. The current study utilized this model to determine the impact of adolescent social isolation on a three-chamber social interaction task both during adolescence and adulthood. We found that while post-weaning isolation does not alter social interaction during adolescence (PND45), it has sex-specific effects on social interaction in young adulthood (PND60), potentiating social interaction in male mice and decreasing it in female mice. As early life stress can activate microglia leading to alterations in neuronal pruning, we next examined the impact of inhibiting microglial activation with daily minocycline administration during the first 3 weeks of social isolation on these changes in social interaction. During adolescence, minocycline dampened social interaction in male mice, while having no effect in females. In contrast, during young adulthood, minocycline did not alter the impact of adolescent social isolation in males, with socially isolated males exhibiting higher levels of social interaction compared to their group housed counterparts. In females, adolescent minocycline treatment reversed the effect of social isolation leading to increased social interaction in the social isolation group, mimicking what is seen in naïve males. Taken together, adolescent social isolation leads to sex-specific effects on social interaction in young adulthood and adolescent minocycline treatment alters the effects of social isolation in females, but not males.
青春期是人类大脑发育的关键时期，在此期间暴露于压力之下会对行为和大脑发育产生持久影响。社会隔离和孤独是特别突出的压力源，尤其会导致女性出现有害的心理健康后果，尽管大多数关于社会隔离的临床前研究是在雄性动物身上进行的。我们实验室开发了一种断奶后青少年社会隔离模型，该模型会导致药物奖赏敏感性增加以及边缘脑区神经元结构改变。当前的研究利用这个模型来确定青少年社会隔离对青春期和成年期三室社会互动任务的影响。我们发现，虽然断奶后隔离在青春期（出生后第45天）不会改变社会互动，但它在成年早期（出生后第60天）对社会互动有性别特异性影响，增强了雄性小鼠的社会互动，而减少了雌性小鼠的社会互动。由于早期生活压力会激活小胶质细胞，导致神经元修剪改变，接下来我们研究了在社会隔离的前3周每天给予米诺环素抑制小胶质细胞激活对这些社会互动变化的影响。在青春期，米诺环素减弱了雄性小鼠的社会互动，而对雌性小鼠没有影响。相比之下，在成年早期，米诺环素并没有改变青少年社会隔离对雄性小鼠的影响，与群居的雄性小鼠相比，社会隔离的雄性小鼠表现出更高水平的社会互动。在雌性小鼠中，青少年期米诺环素治疗逆转了社会隔离的影响，导致社会隔离组的社会互动增加，类似于在未经历过社会隔离的雄性小鼠中观察到的情况。综上所述，青少年社会隔离会对成年早期的社会互动产生性别特异性影响，青少年期米诺环素治疗会改变社会隔离对雌性小鼠的影响，但对雄性小鼠没有影响。
