Correlation between expression of extracellular signal-regulated protein kinase 5 in rat brain and changed capacity of learning and memory of rats with chronic fluorosis

Objective Through observation of the expression and activity of extracellular regulated protein kinase 5 (ERK5) and its relationship with the learning and memory ability in rats with chronic fluorosis, to further study the pathogenesis of chronic fluorosis in nervous system. Methods Thirty SD rats were divided into 3 groups according to body weight by means of a random number table (10 rats in each group, half male and half female). The rats in control group were fed with free drinking tap water containing less than 0.5 mg/L fluoride (NaF); the rats in low fluoride group with 10.0 mg/L fluoride; the rat in high dose fluoride group with 50.0 mg/L fluoride. After 6 months of experiment, rat brain tissue was took, mRNA expression level of ERK5 was detected by real- time fluorescence quantitative PCR (real- time PCR), protein expression level and activity of ERK5 were detected by Western blotting; the learning and memory ability of rats with chronic fluorosis were detected by Morris water maze test. Results The rat in groups exposed to fluoride exhibited different degrees of dental fluorosis and the fluoride content in urine of rats increased gradually with increase of fluoride doses (F = 164.10,P 0.05). The second, third, and forth days of directional navigation experiment, the time of escape latency and the number of crossing the platform between groups were statistically significant (H = 28.20, 29.90, 26.47, 27.23, 35.34, 27.62, allP < 0.01); the fifth day of space exploration experiment, the difference of the time of the first crossing platform and the number of crossing the platform between groups were statistically significant (H = 31.41, 30.80, allP < 0.01); the protein level of phosphor-ERK5 in brain tissue of rats was negatively correlated with the number of the first crossing platform (r = - 0.470,P < 0.01), while positively related to escape latencies at the fifth day of the test (r = 0.591,P < 0.01). Conclusion The changes of ERK5 signaling pathway in rat brain tissue caused by chronic fluorosis are found, which are related to the decrease of learning and memory ability of animals with chronic fluorosis. Key words: Fluorosis; Learning; Memory; Extracellular signal-regulated protein kinase 5