Venlafaxine Improves the Cognitive Impairment and Depression-Like Behaviors in a Cuprizone Mouse Model by Alleviating Demyelination and Neuroinflammation in the Brain
Venlafaxine Improves the Cognitive Impairment and Depression-Like Behaviors in a Cuprizone Mouse Model by Alleviating Demyelination and Neuroinflammation in the Brain
复制标题
文拉法辛通过减轻大脑脱髓鞘和神经炎症来改善 Cuprizone 小鼠模型的认知障碍和抑郁样行为
DOI：
10.3389/fphar.2019.00332
复制
发表时间：
2019-04-05
影响因子：
5.6
通讯作者：
Li, Xin-Min
中科院分区：
文献类型：
--
作者：
Zhang, Yanbo;Bi, Xiaoying;Li, Xin-Min
越来越多的证据表明，髓磷脂缺失和神经炎症是导致重度抑郁症（MDD）和多发性硬化症（MS）患者情绪波动和认知能力下降的共同病理特征。因此，神经炎症的衰减和脱髓鞘的减少成为情绪和认知症状的新出现的治疗策略。抗抑郁药文拉法辛通过其多重神经保护作用已被用于抑郁症和焦虑症。然而，目前尚不清楚文拉法辛是否可以改善髓磷脂完整性和改变大脑炎症状态。通过建立铜酮诱导的急性小鼠脱髓鞘模型，我们研究了文拉法辛对这些方面的保护作用。铜酮喂养的动物表现出认知障碍和情绪障碍，以及髓磷脂丢失和大脑明显的神经炎症。我们目前的研究表明，高剂量的文拉辛减轻了髓磷脂和少突胶质细胞（OLs）的损失，减轻了抑郁样行为，并改善了铜酮喂养动物的认知功能。本研究的数据还表明，文拉法辛减少了铜酮喂养的动物大脑中小胶质细胞介导的炎症。这些发现表明文拉法辛可能通过促进髓磷脂完整性和控制神经炎症来发挥其治疗作用，这可能为MS患者的抑郁和焦虑提供超出症状管理的额外益处。
Growing evidence has implicated that myelin deficits and neuroinflammation are the coexisted pathological features that contribute to the mood swing and cognitive decline in major depressive disorder (MDD) and multiple sclerosis (MS). Therefore, attenuation of neuroinflammation and reduction of demyelination became newly emerging treatment strategies for the mood and cognitive symptoms. Antidepressant venlafaxine has been used in depression and anxiety through its multiple neuroprotective effects. However, it is unclear whether venlafaxine can improve myelin integrity and alter inflammation status in the brain. By using a well-established cuprizone-induced acute mouse model of demyelination, we investigated the protective effects of venlafaxine on these facets. The cuprizone-fed animals exhibited cognitive impairment and mood disturbances together with myelin loss and prominent neuroinflammation in the brain. Our present study showed that a high dose of venlafaxine alleviated the loss of myelin and oligodendrocytes (OLs), mitigated depression-like behaviors, and improved cognitive function in cuprizone-fed animals. Data from the present study also showed that venlafaxine reduced microglia-mediated inflammation in the brains of cuprizone-fed animals. These findings suggest that venlafaxine may exert its therapeutic effects via facilitating myelin integrity and controlling neuroinflammation, which may provide extra benefits to MS patients with depression and anxiety beyond the symptom management.