Effects of high copper diet on cognitive function and hippocampal synaptic protein in rats / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To observe the effects of high copper diet on neurobehavioral functions and synaptic associated protein expression in hippocampus of rats.Methods:Thirty male SD rats were randomly divided into control group and high copper diet group with 15 rats in each group according to the random number table method. The rats in control group were fed with ordinary diet and ordinary water, while the rats in high-copper diet group were fed with high-copper diet containing 1 g/kg copper sulfate and 0.185% copper sulfate deionized water for 12 weeks. The content of copper in serum and hippocampus of rats were detected by inductively coupled plasma-atomic emission spectrometry(ICP-AES) and ICP-mass spectrometry(ICP-MS). The neurobehavioral indicators were detected by stereotypic behavior test, open field test and Morris water maze test. The expression levels of microtubule associated protein 2(MAP2) and growth associated protein 43 (GAP43) in hippocampus were detected by Western blot.SPSS 22.0 software was used for statistical analysis, and two independent sample t-test was used for comparison between the two groups. Results:Compared with the control group, the content of serum copper((1.67±0.69)mg/L, (1.98±0.24)mg/L, t=17.53, P<0.05) and hippocampal free copper((3.52±1.24)mg/g, (4.78±0.57)mg/g, t=10.34, P<0.05) in the high copper diet group increased significantly, and the stereotypic behavior score increased significantly ((0.29±0.08), (2.97±0.72), t=14.33, P<0.01), the number of space crossing in the open field experiment ((153.40±24.73)points, (92.46±19.46)points, t=7.50, P<0.01) and the times of standing((19.34±1.98)times, (10.57±2.71)times, t=10.12, P<0.01) were significantly decreased. The average latency in Morris water maze navigation test was significantly prolonged ((3.14±1.67)s, (8.29±2.26)s, t=7.10, P<0.01), the number of crossing the original platform position in the space exploration test decreased significantly ((7.89±2.48)times, (2.98±1.73) times, t=3.23, P<0.01). Compared with control group, protein levels of GAP43((1.03±0.05), (0.48±0.02), t=39.56, P<0.05)and MAP2((0.93±0.05), (0.30±0.08), t=25.86, P<0.05) of high copper diet group were significantly decreased. Conclusion:High copper diet causes abnormality in a variety of neurobehavioral function indexes in rats, and a decrease in expression of MAP2 and GAP43 at the synaptic interface of hippocampal neurons may be involved in the process of learning and memory impairment in the neurobehavioral functions.