Dilated Virchow-Robin spaces in the hippocampus impact behaviors and effects of anti-depressant treatment in model of depressed rats.

The occurrences of dilated Virchow-Robin spaces (dVRSs) and inflammatory factors were closely related with development of depression and antidepressants. The present study indicated accumulation of inflammatory factors in dVRSs played a practical role in behaviors and the treatment-resistant in rats with depression. Eighty-one male Wistar rats were exposed to chronic unpredictable mild stress (CUMS) until the model was successfully established. According to the detection of dVRSs on 7 T structural magnetic resonance imaging (MRI), rats were divided into two groups (45 CUMS rats and 36 CUMS rats). Subsequently, different antidepressant treatment (nontreat, aspirin, fluoxetine, fluoxetine+aspirin) was given to the two groups, respectively. Sucrose preference test (SPT), forced swim test (FST) and morris water maze (MWM) was used to test the behaviors of rats. ELISA and Western blot was used to determine the levels of inflammatory factors. Compared with the negative control (NC) group, there were obvious behavioral abnormalities and increased inflammatory factors in the CUMS rats. Interestingly, these changes were more significant in the CUMS rats. In addition, the efficacy of fluoxetine was only found in CUMS rats rather than CUMS rats. Meanwhile, behaviors and levels of inflammatory factor in hippocampus were ameliorated in the aspirin group of CUMS rats, and these effects were significantly enhanced in the fluoxetine+aspirin group. The dVRSs in the hippocampus might exacerbate depression-like behaviors and the effects of antidepressant treatment in depressed rats by increasing the levels of inflammatory factors.