Therapeutic effect of curcumin and hippocampal brain-derived neurotrophic factor on a rat model of Alzheimer’s disease / 西安交通大学学报(医学版)

ABSTRACT

ABSTRACTObjective 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 (2×10 5 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 4,2 9 5=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.