Effects of arsenic exposure on mRNA levels of BDNF and TrkB in hippocampus of offspring mice at different developmental stages / 中华地方病学杂志

ABSTRACT

Objective:To investigate the possible mechanism of learning and memory damage induced by arsenic exposure through studying the effects of arsenic exposure on levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinases B (TrkB) in hippocampus of offspring mice at different developmental stages.Methods:Twenty-four pregnant Kunming mice were divided into control (distilled water) group and 15, 30 and 60 mg/L sodium arsenite (NaAsO 2) groups according to random number table method, six mice in each group. The pregnant mice were exposed to NaAsO 2 until weaning. After weaning, the offspring mice were still exposed to NaAsO 2 through drinking water till postnatal day (PND) 40. Morris water maze was used to determine the effects of arsenic exposure on learning and memory ability in PND 40 mice. The body weight of the mice was measured at PND 10, 20 or 40, and brain tissues were taken after the mice were sacrificed and the hippocampus was isolated. The levels of BDNF and TrkB mRNA in the hippocampus of offspring mice were measured by Real-time PCR. Results:There was significant difference in body weight of PND 20 offspring mice among the control, 15, 30 and 60 mg/L NaAsO 2 groups [(14.42 ± 1.88), (13.50 ± 1.38), (13.00 ± 1.14), (11.75 ± 0.82) g, F = 4.000, P < 0.05], the body weight of offspring mice in 60 mg/L NaAsO 2 group decreased significantly than that in control group( P < 0.05); there was significant difference in body weight of PND 40 offspring mice among groups [(38.58 ± 2.35), (37.17 ± 1.78), (35.67 ± 1.69), (33.83 ± 1.47) g, F = 7.248, P < 0.05], the body weights of offspring mice in 30 and 60 mg/L NaAsO 2 groups were significantly lower than that in control group, and the body weight of PND 40 offspring mice in 60 mg/L NaAsO 2 group was significantly lower than that in 15 mg/L NaAsO 2 group ( P < 0.05); the results of Morris water maze showed that there were significant differences in the escape latency of offspring mice among groups since 3 - 5 days of training ( F = 3.380, 6.788, 7.240, P < 0.05), the escape latency of offspring mice in NaAsO 2 groups [(67.76 ± 6.45), (71.47 ± 12.19), (73.96 ± 10.42), (58.63 ± 9.24), (60.20 ± 3.74), (67.96 ± 15.41) s] was significantly longer than that in control group [(52.83 ± 8.33), (43.39 ± 8.98) s] since 4 - 5 days of training ( P < 0.05); on the other hand, in the probe trail, there was significant difference in time spent in the target quadrant of offspring mice among groups ( F = 5.709, P < 0.05), time spent in the target quadrant of offspring mice in 30 and 60 mg/L NaAsO 2 groups [(18.85 ± 3.97), (16.90 ± 1.62) s] was significantly less than that in control group [(24.48 ± 3.18) s, P < 0.05]; there was significant difference in BDNF mRNA levels (1.00 ± 0.05, 0.98 ± 0.06, 0.85 ± 0.06, 0.68 ± 0.03) of PND 20 mice among groups ( F = 9.368, P < 0.05), BDNF mRNA level of mice exposed to 60 mg/L NaAsO 2 was significantly lower than that in control, 15 and 30 mg/L NaAsO 2 groups ( P < 0.05); there was significant difference in BDNF mRNA levels (1.00 ± 0.03, 0.75 ± 0.02, 0.76 ± 0.03, 0.73 ± 0.06) of PND 40 mice among groups ( F = 3.998, P < 0.05), and that of PND 40 mice exposed to NaAsO 2 decreased significantly than that in control group ( P < 0.05); there was significant difference in TrkB mRNA levels (1.00 ± 0.08, 0.71 ± 0.02, 0.73 ± 0.02, 0.68 ± 0.09) of PND 20 mice among groups ( F = 16.158, P < 0.05), and that of PND 20 mice exposed to NaAsO 2 were significantly lower than that in control group ( P < 0.05). Conclusion:Arsenic exposure could decrease the mRNA levels of BDNF and TrkB in the hippocampus of offspring mice, which may affect the ability of learning and memory.