Brakel Kiralyn, Aceves Miriam, Garza Aryana, Yoo Chaeyoung, Escobedo Gabriel, Panchani Nishah, Shapiro Lee, Hook Michelle
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University, Medical Research and Education Building, Ste. 1005 8447 Riverside Pkwy, Bryan, TX, 77807, United States.
Texas A&M Institute of Neuroscience, Texas A&M University, Interdisciplinary Life Sciences Building, Rm 3148, 3474, TAMU, College Station, TX, United States.
Brain Behav Immun Health. 2021 Apr 19;14:100258. doi: 10.1016/j.bbih.2021.100258. eCollection 2021 Jul.
Following spinal cord injury, 18-26% of patients are diagnosed with depressive disorders, compared to 8-12% in the general population. As increased inflammation strongly correlates with depression in both animal and human studies, we hypothesized that the immune activation inherent to SCI could increase depression-like behavior. Thus, we proposed that reducing immune activation with minocycline, a microglial inhibitor, would decrease depression-like behavior following injury. Male Sprague-Dawley rats were given minocycline in their drinking water for 14 days following a moderate, mid-thoracic (T12) spinal contusion. An array of depression-like behaviors (social activity, sucrose preference, forced swim, open field activity) were examined prior to injury as well as on days 9-10, 19-20, and 29-30 post-injury. Peripheral cytokine levels were analyzed in serum collected prior to injury and 10 days post-injury. Hierarchical cluster analysis divided subjects into two groups based on behavior: depressed and not-depressed. Depressed subjects displayed lower levels of open field activity and social interaction relative to their not-depressed counterparts. Depressed subjects also showed significantly greater expression of pro-inflammatory cytokines both before and after injury and displayed lower levels of hippocampal neurogenesis than not-depressed subjects. Intriguingly, subjects who later showed depressive behaviors had higher baseline levels of the pro-inflammatory cytokine IL-6, which persisted throughout the duration of the experiment. Minocycline, however, did not affect serum cytokine levels and did not block the development of depression; equal numbers of minocycline versus vehicle-treated subjects appeared in both phenotypic groups. Despite this, these data overall suggest that molecular correlates of inflammation prior to injury could predict the development of depression after a physical stressor.
脊髓损伤后，18%-26%的患者被诊断患有抑郁症，而普通人群的这一比例为8%-12%。由于在动物和人体研究中，炎症增加都与抑郁症密切相关，我们推测脊髓损伤固有的免疫激活可能会增加类似抑郁的行为。因此，我们提出用小胶质细胞抑制剂米诺环素降低免疫激活，会减少损伤后类似抑郁的行为。对雄性Sprague-Dawley大鼠在中度胸段（T12）脊髓挫伤后，给予其饮用水中的米诺环素，持续14天。在损伤前以及损伤后第9-10天、19-20天和29-30天，检测一系列类似抑郁的行为（社交活动、蔗糖偏好、强迫游泳、旷场活动）。分析损伤前和损伤后10天采集的血清中的外周细胞因子水平。层次聚类分析根据行为将受试者分为两组：抑郁组和非抑郁组。与非抑郁的对应组相比，抑郁组的旷场活动和社交互动水平较低。抑郁组在损伤前后促炎细胞因子的表达也显著更高，并且海马神经发生水平低于非抑郁组。有趣的是，后来表现出抑郁行为的受试者促炎细胞因子IL-6的基线水平较高，且在整个实验过程中持续存在。然而，米诺环素并未影响血清细胞因子水平，也未阻止抑郁症的发展；在两个表型组中，米诺环素治疗组和溶剂治疗组的受试者数量相等。尽管如此，这些数据总体表明，损伤前炎症的分子关联可能预测身体应激源后抑郁症的发展。
