Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Robarts Research Institute, University of Western Ontario, London, Canada.
Brain Struct Funct. 2023 Dec;228(9):2051-2066. doi: 10.1007/s00429-023-02705-z. Epub 2023 Sep 10.
Chronic social stress is a significant risk factor for several neuropsychiatric disorders, mainly major depressive disorder (MDD). In this way, patients with clinical depression may display many symptoms, including disrupted social behavior and anxiety. However, like many other psychiatric diseases, MDD has a very complex etiology and pathophysiology. Because social isolation is one of the multiple depression-inducing factors in humans, this study aims to understand better the link between social stress and MDD using an animal model based on social isolation after weaning, which is known to produce social stress in mice. We focused on cellular composition and white matter integrity to establish possible links with the abnormal social behavior that rodents isolated after weaning displayed in the three-chamber social approach and recognition tests. We used the isotropic fractionator method to assess brain cellularity, which allows us to robustly estimate the number of oligodendrocytes and neurons in dissected brain regions. In addition, diffusion tensor imaging (DTI) was employed to analyze white matter microstructure. Results have shown that post-weaning social isolation impairs social recognition and reduces the number of neurons and oligodendrocytes in important brain regions involved in social behavior, such as the anterior neocortex and the olfactory bulb. Despite the limitations of animal models of psychological traits, evidence suggests that behavioral impairments observed in patients might have similar biological underpinnings.
慢性社会压力是几种神经精神疾病的重要风险因素，主要是重度抑郁症（MDD）。因此，患有临床抑郁症的患者可能会表现出许多症状，包括社交行为中断和焦虑。然而，与许多其他精神疾病一样，MDD 的病因和发病机制非常复杂。由于社会隔离是人类多种诱发抑郁的因素之一，因此本研究旨在使用基于断奶后社会隔离的动物模型更好地了解社会压力与 MDD 之间的联系，该模型已知会在小鼠中产生社会压力。我们专注于细胞组成和白质完整性，以建立与断奶后隔离的啮齿动物在三室社交接近和识别测试中表现出的异常社交行为之间的可能联系。我们使用各向同性分数器方法评估脑细胞数量，这使我们能够可靠地估计解剖脑区中的少突胶质细胞和神经元数量。此外，还采用弥散张量成像（DTI）来分析白质微观结构。结果表明，断奶后社会隔离会损害社交识别能力，并减少参与社交行为的重要脑区（如前新皮质和嗅球）中的神经元和少突胶质细胞数量。尽管心理特征的动物模型存在局限性，但有证据表明，在患者中观察到的行为障碍可能具有相似的生物学基础。
