Background Dibutyl phthalate (DBP) is a class of typical phthalate ester pollutants. Epidemiological studies and animal experiments have shown that DBP can cause neurobehavioral changes in animals, and the mechanism may be related to the expression of extracellular regulated protein kinase (ERK) in hippocampal neurons. In addition, curcumin (Cur) has attracted much attention recently because of its active role in the potential treatment of various central nervous diseases, but its effect on learning and memory impairment induced by DBP remains unclear.
Objective This experiment detects the effects of Cur on the oxidative stress levels and expressions of ERK pathway related proteins in hippocampus of KM young mice exposed to DBP, and explores the effects of Cur on decreased learning and memory induced by DBP and the underlying mechanism.
Methods Thirty-two young male KM mice were randomly divided into four groups:saline group, 50 mg/(kg·d) DBP group, 2.5 mg/(kg·d) Cur group, and DBP+Cur group. After 28 consecutive days of exposure, the escape latencies of the experimental groups were tested by Morris water maze; reactive oxygen species (ROS), malondialdehyde (MDA), and total antioxidant capacity (T-AOC) in hippocampus were determined; the levels of ERK pathway related protein, phosphorylated-ERK (p-ERK), and early brain injury neurofilament proteins (c-Fos and c-Jun) were detected by Western blotting; the pathological alterations in the CA1 area of hippocampus were observed after HE staining.
Results Compared with the control group, the escape latency of young mice in the DBP group was prolonged to (46.96±4.37)s (P=0.007); the levels of ROS and MDA in brain was increased to (6 387.00±84.80) U/well and (1.65±0.10) μmoL/g (in protein) (P=0.006, P=0.015), respectively; the level of T-AOC was decreased to (0.55±0.05) U/mg (P=0.016); the expression levels of p-ERK, c-Fos, and c-Jun in the hippocampus were increased significantly (P=0.002, P=0.001, P=0.003); the HE stained specimens of hippocampal tissues showed identifiable pathological changes in CA1. After the Cur treatment, compared with the DBP group, the escape latency of the DBP+Cur group was decreased to (37.79±5.72) s (P=0.048); the levels of ROS and MDA were decreased to (5 934.80±38.07) and (1.10±0.08) μmoL/g (in protein) (P=0.032, P=0.014), respectively; the expression levels of p-ERK, c-Fos, and c-Jun were decreased (P=0.040, P=0.009, P=0.008); less cells with pathological changes were observed in hippocampal CA1.
Conclusion Cur can ameliorate the effects of decreased learning and memory induced by DBP, and the mechanism may be related to the down-regulated oxidative stress and ERK pathway related protein expression levels.
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