Role of rapamycin target protein in lanthanum-induced injury of cerebral cortical neurons in offspring rats / 中华地方病学杂志

ABSTRACT

Objective:To investigate the role of rapamycin target protein (mTOR) in lanthanum-induced injury of cerebral cortical neurons in offspring rats, and the effect on brain development, learning and memory ability of offspring rats.Methods:Thirty-two adult female and 32 male Wistar rats, were randomly divided into 4 groups according to their body weight, with 16 rats in each group (half female and half male). Female rats were fed with different amounts of lanthanum chloride[0.0 (control), 2.5, 5.0, 10.0 g/L], while male rats drank normal water. Female and male rats were mated in cages at a ratio of 1∶1. Female rats began to be exposed to lanthanum from pregnancy, while their offspring were exposed to lanthanum until 4 weeks after weaning. Morris water maze experiment was carried out in the 4 groups of offspring rats, and the effects of lanthanum on learning and memory were observed by space exploration. The cerebral cortex of offspring rats was taken, and the amount of Nissl body was observed under microscope after Nissl staining. The expression of mTOR mRNA in offspring rats cerebral cortex nerve cells was measured by real-time quantitative PCR. Western blotting was used to detect the protein content of p-mTOR in offspring rats cortical neurons.Results:Compared with the control group, the body weight of offspring rats exposed to lanthanum at 2.5, 5.0 and 10.0 g/L was significantly decreased [(121.75 ± 11.20), (110.00 ± 11.59), (98.88 ± 7.95) and (85.63 ± 7.25) g, P < 0.05], and the brain tissue coefficient and cortical coefficient were significantly increased [(1.43 ± 0.10)%, (1.56 ± 0.18)%, (1.66 ± 0.14)%, (1.89 ± 0.16)%; (0.86 ± 0.08)%, (0.94 ± 0.08)%, (1.01 ± 0.07)%, (1.08 ± 0.09)%, P < 0.05]. The brain weight [(1.63 ± 0.05), (1.61 ± 0.03) g] of 5.0 and 10.0 g/L lanthanum-exposed groups were significantly lower than those in the control group and 2.5 g/L lanthanum-exposed group [(1.73 ± 0.06), (1.70 ± 0.06) g, P < 0.05]. Compared with the control group (53.25 ± 9.93), the amounts of Nissl body in cerebral cortical neurons in different lanthanum-exposed groups (36.13 ± 3.98, 27.50 ± 5.21, 13.63 ± 5.93) were significantly decreased ( P < 0.05). The results of space exploration experiment showed that compared with the control group [(5.75 ± 1.98) times, (10.69 ± 2.96) s, (3.75 ± 1.28) times], the times of entering the target quadrant [(3.63 ± 1.41) times] and the stay time in the target quadrant [(5.12 ± 2.09) s] in 10.0 g/L lanthanum-exposed group were significantly reduced ( P < 0.05), and the times of entering the platform [(1.88 ± 0.84), (1.13 ± 1.12) times] in 5.0 and 10.0 g/L lanthanum-exposed groups were significantly reduced ( P < 0.05). There were significant differences in mTOR mRNA (1.00 ± 0.28, 0.74 ± 0.19, 0.58 ± 0.13, 0.45 ± 0.29) and p-mTOR protein expression levels (0.69 ± 0.07, 0.33 ± 0.06, 0.30 ± 0.04, 0.17 ± 0.03) in cortical tissues ( F = 8.33, 139.12, P < 0.05). Conclusion:Lanthanum exposure can damage cortical neurons, affect the brain development of offspring rats, reduce the expression of mTOR mRNA and p-mTOR protein in the brain of offspring rats, reduce the ability of space exploration and observation, resulting in the decline of learning and memory ability of offspring rats.