Venlafaxine Improves the Cognitive Impairment and Depression-Like Behaviors in a Cuprizone Mouse Model by Alleviating Demyelination and Neuroinflammation in the Brain

Frontiers in Pharmacology

Xiaoying Bi¹  Jacob Cohen²  Junhui Wang³  Zelan Wei⁴  Olubunmi Adebiyi⁴  Ali Mooshekhian⁴  Yanbo Zhang⁴  Xin-Min Li⁵  Fei Wang⁶ 

[1] Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China;Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada;Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada;Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada;Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada;Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China;

关键词: venlafaxine;    cuprizone;    demyelination;    cognition;    major depressive disorder;    oligodendrocyte;   

DOI  :  10.3389/fphar.2019.00332

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown