抄録
In recent years, dysfunctional mastication, which is resulted from decreased number of residual teeth, use of unsuitable dentures, or reduced biting force, has been suggested to be related to the development of senile dementia. Recently, in senescence-accelerated mice (SAMP8 mice), we have studied the involvement of masticatory dysfunction, e.g. cut off of the upper molar teeth, extract of the upper molar teeth, or cut of the one side of the masseteric nerve, in the senile process of learning and memory. First, we found that conditions of such dysfunctional mastication progress age-related deficits in spatial memory storage in a water maze test and in hippocampal pyramidal neurons. These pathological phenomena were begun to occur in middle-aged mice, suggesting that masticatory disfunction may lead to hippocampal pathological changes in the elderly.
Second, it was found that cutting off the upper molar teeth causes a reduction in the protein product, Fos, of the immediate early gene, c-fos, in the hippocampal CA1 subfield. Interestingly, both the suppression of memory storage ability and the decrease in Fos induction in this subfield induced by cutting off the upper molars were considerably improved by restoring the lost molars with artificial crowns, suggesting that normal mastication may be an important factor in maintaining normal hippocampal activities.
Third, in biochemical and immunohistochemical studies examining the effect of masticatory dysfunction on age-related changes in the septohippocampal cholinergic system, we have foundthat, in aged mice, masticatory disfunction induces a decrease in acetylcholine release and choline acetyltransferase activity in the hippocampus and a reduction in the number of choline acetyltransferase-immunopositive neurons in the medial septal nucleus. However, these effects were not seen in young mice, implying that dysfunctional mastication may enhance an age-related decline in the septohippocampal cholinergic system.
Finally, stress may be linked to hippocampal pathological changes induced by masticatory dysfunction. As expected, in the aged mice, conditions under masticatory dysfunction brought about a chronic elevation in plasma corticosterone levels. However, pretreatment with metyrapone, which suppresses the stress-induced rise in this hormone levels, prevented dysfunctional mastication-induced increase in plasma corticosterone levels, reduction in hippocampal pyramidal neuron numbers, and impairment of spatial memory. These findings suggest a link between the masticatory dysfunction and the glucocorticoid response, which may be involved in deficits in learning and memory and hippocampal neuronal death.
In conclusion, we suggest that normal mastication may be effective in preventing senile dementia by maintaining normal function in the hippocampus, which is the most sensitive region to aging processes.
