[Establishment and evaluation of a rat model of diabetes comorbid depression and its expression of glial fibrillary acidic protein in the brain].

OBJECTIVE: To establish and evaluate a rat model of diabetes comorbid depression, and observe alterations in expression of glial fibrillary acidic protein (GFAP) in several cerebral regions.

METHODS: Eighteen Wistar rats were randomly divided into three groups, the control group (group CON, n=6), the diabetes mellitus group (group DM, n=6), and the diabetes comorbid depression group (group DD, n=6). Rats of group DM and group DD were injected intraperitoneally with STZ (64 mg/kg), the control rats received sham injections of citrate buffer alone. Group DD was then exposed to chronic unpredictable mild stress for 28 days. All rats were submitted to the open-field test and Morris water maze test immediately after the CUMS procedure. After brain tissue collection, the expression of GFAP in bilateral frontal cortex, hippocampus and hypothalamus were measured by immunohistochemistry.

RESULTS: Rats of group DD and group DM exhibited classic diabetic signs of weight loss, hyperphagia, polydipia, gloomy hair and increasing urine and stool, group DD showed mental fatigue and slow response.The STZ-treated groups showed high blood glucose level (>33.3 mol/L) compared to the control group throughout the study. Group DD ((176± 11), (157±8), (154± 12)g)and group DM ((176±10), (161±8), (160±13)g)showed decline on body weight, whereas group CON ((245±14), (276±21), (314±25)g)showed continuously elevated body weight 0, 14, 28 days after CUMS.In behavioral tests, group DD ((4.1±3.1), (115±73), (26±13))showed reduced total traveling distance, activity time and times of locomotion compared to group CON ((9.3±3.2), (200±53), (40±11), P<0.05). Throughout the probe trial of Morris water maze test, group DD and group DM ((0.5±0.5), (0.5±0.6))performed less times of crossing the former platform area compared to group CON ((2.6±2.2), P<0.05). The mean optical density (MOD) of GFAP positive cells in frontal cortex, hippocampus and hypothalamus of group DD ((0.18±0.03), (0.19±0.02), (0.21±0.02)) were decreased compared with group DM ((0.26±0.03), (0.27±0.03), (0.30±0.04), P<0.01), but increased compared with group CON ((0.13±0.04), (0.15±0.02), (0.16±0.03), P<0.05 or P<0.01).

CONCLUSION: Combination of intraperitoneally STZ injection and proper CUMS procedure can successfully build a rat model of diabetes comorbid depression. The expression of GFAP in bilateral frontal cortex, hippocampus and hypothalamus of group DD is significant different form group DM and group CON, which is helpful for understanding the pathogenesis of diabetes comorbid depression.