In order to reveal the mechanism of the decreased ability of learning and memory induced by chronic fluorosis, nicotinic acetylcholine receptors (nAChRs) and the pathway of extracellular signal regulated protein kinase (ERK1/2) were investigated by using the rats fed with different concentrations of sodium fluoride for 6 months. Spatial learning and memory of the rats were evaluated by Morris Water Maze test. The expressions of nAChRs, ERK1/2 and mitogen-induced extracellular kinase (MEK1/2) at protein and mRNA levels were detected by Western blotting and Real-time PCR, respectively. The results showed that as compared with controls, the learning and memory capacity in the rats with fluorosis was decreased. The protein expressions of α7 and α4 nAChR subunits in rat brains with fluorosis were decreased by 35% and 33%, whereas the corresponding receptor subunit mRNAs didn’t exhibit any changes. The increases of phospho- and total- ERK1/2 as well as phospho-MEK1/2 at the protein levels were found in the brains of rats with fluorosis as compared to controls, and no difference of ERK1/2 mRNA was found. In addition, the activation rate of phospho-ERK1/2 was decreased in the brains affected with fluorosis. The modifications of nAChRs and ERK1/2 pathway might be connected with the molecular mechanisms in the decreased capacity of learning and memory of the rats with fluorosis.
Neurotox Res. 2009 Dec 3. [Epub ahead of print]
Memory Impairment Induced by Sodium Fluoride is Associated with Changes in Brain Monoamine Levels.
Pereira M, Dombrowski PA, Losso EM, Chioca LR, Da Cunha C, Andreatini R
Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, Curitiba, Brazil.
Previous studies suggest that sodium fluoride (NaF) can impair performance in some memory tasks, such as open-field habituation and two-way active avoidance. In the present study, we evaluated the effect of NaF intake (100 ppm in drinking water for 30 days) and its short-term (15 days) withdrawal on open-field habituation and brain monoamine level. Adult male rats were allocated to three groups: tap water (NaF 1.54 ppm) for 45 days (control group); 15 days of tap water followed by NaF for 30 days; and NaF for 30 days followed by 15 days of tap water. The results showed that NaF impairs open-field habituation and increases noradrenaline (NA) and serotonin (5-HT) in the striatum, hippocampus and neocortex. Dopamine (DA) increase was restricted to the striatum. Short-term NaF withdrawal did not reverse these NaF-induced changes, and both NaF treatments led to a mild fluorosis in rat incisors. No treatment effect was seen in body weight or fluid/water consumption. These results indicate that sodium fluoride induces memory impairment that outlasts short-term NaF withdrawal (2 weeks) and may be associated with NA and 5-HT increases in discrete brain regions.