Zhang Lin, An Li-Ting, Qiu Yan, Shan Xiao-Xiao, Zhao Wen-Li, Zhao Jing-Ping, Li Le-Hua, Lang Bing, Wu Ren-Rong
Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Mental Disorders, Changsha, China.
Front Psychiatry. 2019 Jul 16;10:497. doi: 10.3389/fpsyt.2019.00497. eCollection 2019.
Bipolar disorder (BD) is a chronic and refractory disease with high probability of morbidity and mortality. Although epidemiological studies have established a strong association between BD and immune dysfunction, the precise etiology is still debatable, and the underpinning mechanism remains poorly investigated and understood. In the present study, manic-like symptoms of BD were induced in rats after intracerebroventricular administration of ouabain. Aspirin, a commonly used anti-inflammatory agent, was used to treat the induced manic-like symptoms and inflammation. Concentrations of a spectrum of inflammatory cytokines were examined by enzyme-linked immunosorbent assay in both plasma and brain tissues, and expression of Toll-like receptors 3 and 4 were determined in rat brains. Locomotor activity was monitored with open-field test to assess the effects of ouabain challenge and to evaluate the treatment efficacy of aspirin. Ouabain administration recapitulated many mania-like features such as increased stereotypic counts, traveling distance in open-field test, and decreased expression of brain-derived neurotrophic factor, interferon gamma, and Toll-like receptor 3, which were frequently found in patients with BD. These abnormalities could be partially reversed by aspirin. Our findings suggest that aspirin could be used as a promising adjunctive therapy for BD.
双相情感障碍（BD）是一种慢性难治性疾病，具有较高的发病率和死亡率。尽管流行病学研究已证实BD与免疫功能障碍之间存在密切关联，但其确切病因仍存在争议，相关潜在机制仍未得到充分研究和理解。在本研究中，通过脑室内注射哇巴因在大鼠中诱导出BD的躁狂样症状。阿司匹林是一种常用的抗炎药物，用于治疗诱导出的躁狂样症状和炎症。采用酶联免疫吸附测定法检测血浆和脑组织中一系列炎性细胞因子的浓度，并测定大鼠脑中Toll样受体3和4的表达。通过旷场试验监测运动活动，以评估哇巴因激发的影响并评价阿司匹林的治疗效果。注射哇巴因重现了许多躁狂样特征，如刻板行为计数增加、旷场试验中的行进距离增加，以及脑源性神经营养因子、干扰素γ和Toll样受体3的表达降低，这些特征在BD患者中经常出现。这些异常情况可被阿司匹林部分逆转。我们的研究结果表明，阿司匹林有望作为BD的辅助治疗药物。
