Abstract:
Background Fluorine can enter human body through drinking water, air, food, and other media. Excessive fluorine not only causes bone damage, but also passes through blood-brain barrier and accumulates in brain tissues, causing nervous system injury, and consequently presenting decreased neuronal connectons, abnormal synaptc functon, and impaired spatal learning and memory, ect.
Objective This experiment is designed to explore the effects of chronic fluoride exposure on hippocampal structure and spatal learning and memory in F2 rats.
Methods Sixteen clean SD pregnant rats were randomly divided into four groups, with four rats in each group:control (drinking water) and 60, 120, and 240 mg/L NaF groups. The pregnant rats were treated with NaF through drinking water from gestatonal day 0 to postnatal day 21 (PND21) of F1 rats. The F1 rats were treated with corresponding concentratons from PND22 to PND90, and six F1 rats (female:male=2:1) were randomly caged and followed the same protocol untl PND21 of F2 rats. Eight F2 rats (female:male=1:1) were randomly selected from each group and treated with corresponding concentratons from PND22 to PND60. The spatal learning and memory ability of the F2 rats was tested by Morris water maze and light-dark box experiment. The levels of fluorine in the F2 rat brain and 24-h urine samples were measured. The hippocampal pathological changes were observed by HE staining and electron microscopy afer the designed exposure.
Results Compared with the control group, the weights of the F2 rats of the 120 and 240 mg/L NaF treatment groups afer eight weeks were decreased. Compared with the control group(7.06±0.79) μg/g, (1.89±0.23) μg/L, the brain fluorine(14.23±1.86), (18.15±1.98), (28.74±2.19) μg/g and urinary fluorine levels(11.36±0.91), (15.30±0.26), (18.67±2.01) μg/L of the NaF treated F2 rats were increased (P < 0.01). In the Morris water maze test, compared with the control group, the escape latencies in the 120 and 240 mg/L NaF treated F2 rats on the second day and third day and in all NaF treated F2 rats on the fourth day were increased (P < 0.05, P < 0.01); the tme to reach the original platorm was prolonged while the frequency of platorm crossings were decreased in the 120 and 240 mg/L NaF treated F2 rats (P < 0.05, P < 0.01). In the light-dark box experiment, the tme in the dark box(157.25±33.17), (209.38±10.98) s and the percentage of tme in the dark box(52.42±11.06)%, (69.79±3.67)% of the 120 and 240 mg/L NaF treated F2 rats were higher than those of the control group (P < 0.01), while the number of transitons of the 240 mg/L NaF treated F2 rats was reduced (P < 0.01). According to the optcal microscopy observaton with HE staining, compared with the control group, the NaF treated groups showed hippocampal neurons with nuclear pyknosis, hyperchromasia nucleus, and loss of structure. The electron microscopy observaton showed mitochondrial swelling, as well as Golgi and endoplasmic retculum expansion in hippocampal neurons of the NaF treated groups.
Conclusion Contnuous fluorine exposure can damage the hippocampal neuron structure and reduce spatal learning and memory of F2 rats.
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