Objective: To investigate the expression of extracellular signal-regulated protein kinase (ERK1/2) pathway in rat brains with fluorosis and the effects of fluoride on learning and memory of the rats, and to reveal the mechanisms of damaged nervous system resulted from the toxicity of the ion. Methods: Seventy-two SD rats were divided into 3 groups and 24 rats were in each group. Three groups were fed respectively with different concentrations of fluoride (NaF) for 6 months to establish rat models with fluorosis. Controls were fed with tap water (NaF < 0.5 mg/L); lower and higher concentration group were fed with water containing NaF(5, 50 mg/L). Animals are sacrificed after 6 months of treatment with fluoride and the dissected brains were kept for analysis. The protein levels of ERK1/2 in rat brains were detected by Western-blotting and the mRNA level by RT-PCR. The spatial learning and memorizing ability was measured by Morris water maze test. Results: The ERK1/2 protein in control group, lower and higher concentration group was 0.944 + 0.10,1.253 ± 0.02,1.953 ± 0.07, the differece being statistieally sighificant between any two groups (P < 0.05). The phospho-ERK1/2 protein in control group, lower and higher concentration group was 0.73 ± 0.08,0.77 ± 0.07, 1.28 ± 0.11, the differece being statistieally sighificant between any two groups (P < 0.05); the activation rate of phospho-ERK1/2 in lower and higher concentration group [(68.4 ± 3.8)%, (64.1 ± 3.2)%] was decreased compared to control group[(82.3 ± 10.7)%], the differece being significant (P < 0.05). In the navigation trial, longer escape latencies of lower concentration group on the second, the third, the fifth and the sixth day were observed[(46.0 ± 8.0), (24.0 ± 2.7), (8.9 ± 5.3), (7.4 ± 4.1)s] compared to the control[(39.3 ± 6.9), (19.1 ± 9.1), (8.3 ± 3.4), (4.8 ± 2.7)s], the differece being significant(P < 0.05 or < 0.01); the similar results were also observed in the higher concentration group[(36.9 ± 16.8),(37.7 ± 12.9), (19.7 ± 7.6),(12.2 ± 5.7)s], and the escape latencies of the higher concentration group on the third, the fifth and the sixth day were longer than that in lower concentration group. In the probe test, the rats took more time to reach the first cross in lower and higher concentration group[(1.17 ± 0.75),(4.18 ± 1.10)s] than control group[(5.89 ± 0.56)s], the differece being significant(P < 0.05 or < 0.01); stayed shorter[(17.05 ± 4.25), (18.20 ± 4.57)s] than control [(25.37 ± 5.65)s] in platform area (P < 0.01); the activation rates of ERK1/2 were directly correlated with the time taken to reach the first cross platform located in the probe test (r = 0.364, P < 0.05) and the activation rates were also directly correlated with the escape latencies on the sixth day (r = 0.497, P < 0.05). Conclusion: Long-term exposure of excessive fluoride induces the change of expression and activating rate of the ERK1/2 in rat brains, leading to the decreased capacity of learning and memory.

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