Behaviors and brain glucose metabolism in a rat hyperlipidemia model with depression from chronic unpredictable mild stress

Abstract

To explore the behaviors and brain glucose metabolism in a rat hyperlipidemia model with depression from chronic unpredictable mild stress (CUMS). A total of 30 rats were randomly divided into control (CON), high-fat diet (HFD) and double model factor (DMF) groups (n = 10 each). For HFD model, a high-lipid feed was provided for 13 weeks; for DMF model, a high-lipid feed for 9 weeks was followed by CUMS for 4 weeks.Serum lipids, sucrose test and brain glucose metabolism were individually measured at baseline, before and after CUMS. (1) Serum lipids: total cholesterol ((2.67 ± 0.04), (2.68 ± 0.02) mmol/L) and low density lipoprotein ((1.08 ± 0.03), (1.06 ± 0.01) mmol/L) of HFD and DMF groups were both significantly higher than those of CON group ((1.78 ± 0.12), (0.79 ± 0.04) mmol/L, all P < 0.01).However, high density lipoprotein ((0.89 ± 0.04), (0.87 ± 0.03) mmol/L) of HFD and DMF groups was significantly lower than those of CON group ((1.08 ± 0.22) mmol/L, all P < 0.01) at week 9.(2) Sucrose test: As compared with CON group, there was no statistical significant difference in sucrose relative intake (P = 0.356).However, the differences were statistically significant in relative water intake and sucrose preference (all P < 0.01) at Week 9 in HFD group. At Week 13, water relative intake increased ((15.44 ± 0.57) mg/kg, P < 0.01) and sucrose relative intake and sucrose preference significantly decreased in HFD group ((30.54 ± 0.56) mg/kg, (74.37 ± 0.66)%, all P < 0.01). As compared with CON group, CUMS gradually reduced the relative intake of sucrose solution during CUMS periods in DMY rats (all P < 0.01). As compared with HFD rats, water relative intake, sucrose relative intake and sucrose preference decreased in DMF group (all P < 0.01).(3) Brain glucose metabolism: On 18F-fluorodeoxyglucose micro positron emission tomography, thalamus and striatum were deactivated in HFD group at Week 13 versus Week 9 (all P < 0.01).Hypothalamus and insular cortex were activated while hippocampus and entorhinal cortex deactivated after CUMS in DMY group (all P < 0.01). When hyperlipidemia and depression co-exist, there are significant changes of brain glucose metabolism in many emotion-related brain regions.