Therapeutic effect of curcumin and hippocampal brain-derived neurotrophic factor on a rat model of Alzheimer's disease

Objective: To study the effect of curcumin on the learning and memory ability in a rat model of Alzheimer's disease (AD). Methods: AD rat model was prepared using intraventricular injection of Aβ1-42. Curcumin was acutely (single injection before the behavioral tests) or chronically (injected for 6 consecutive days) injected intraperitoneally at doses of 50, 100 or 300 mg/kg. Brain-derived neurotrophic factor (BDNF) protein (1 μg/side) or BDNF shRNA (2×10⁵ units/side) was infused into the hippocampus. The behavioral changes in Y-maze, open field test and Morris water maze and the expression of BDNF in the hippocampus were analyzed. Results: Acute treatment with curcumin had no significant effects on the spontaneous alteration, locomotor activity or water maze latency of AD rats. AD rats treated chronically with curcumin (300 mg/kg) showed significant elevation in the spontaneous alternation (P<0.000 1) in Y-maze and memory ability in the water maze test (P<0.05) compared with those in the saline group. Chronic treatment with 100 and 300 mg/kg of curcumin induced an increased level of BDNF in the hippocampus as compared with the saline controls (P<0.05 and <0.000 1). Intrahippocampal injection of BDNF significantly decreased the escape latency of AD rats in the water maze (F_4,295=5.813, P<0.01). Rats chronically injected with curcumin combined with shBDNF showed no difference in the swimming time in II quadrant as compared with saline controls (P=0.657). However, rats in 100 mg/kg curcumin group, BDNF group and sham group had significantly increased swimming time than the saline controls (P<0.05, P<0.05 and P<0.000 1, respectively). Conclusion: Curcumin may activate the downstream signaling pathways by upregulating the expression of BDNF and ultimately contribute to the improvement of learning and memory in AD rats.