Summary:We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, spatial learning in the water maze, fos induction, hippocampal neuron number, expression of glucocorticoid receptors (GR) and glucocorticoid receptor messenger ribonucleic acid (GRmRNA) in hippocampus and inhibitor of glucocorticoid (metyrapone).Bite-raised aged mice had significantly greater plasma corticosterone levels than age-matched control mice as well as impaired spatial memory and decreased Fos induction and a number of neurons in hippocampus. GR and GRmRNA expressions were significantly decreased in aged bite-raised mice compared with age-matched control mice. Pretreatment with metyrapone inhibited not only the bite-raised induced increase in plasma corticosterone levels, but also the reduction in the number of hippocampal neurons and impaired spatial learning.These datas suggest that the bite-raised condition may enhance the aging process in hippocampus, thereby leading to impairment of spatial memory by stress.

We evaluated whether long-term tooth loss induces functional and morphologic changes in the hippocampus in senescence-accelerated mice (SAMP8) maintained until old age after tooth extraction shortly after tooth eruption. First, to examine whether early tooth loss acts as a stressor, plasma concentration was measured as an index of stress. Plasma corticosterone concentration was significantly higher in old or mature mice with tooth extraction than in the age-matched controls. Plasma corticosterone concentration did not differ between the young tooth extraction and their age-matched control groups. Next, hippocampal function was assessed by evaluating spatial memory performance in the Morris water maze. In the Morris water maze learning and memory trials was significantly slower in the mature or old tooth extraction groups compared with the age-matched controls. There was no significant difference, however, between the young tooth extraction and control groups. Finally, hippocampal neuronal morphology was assessed by counting Nisslstained cells. The number of hippocampal neurons was significantly reduced in the CA3 region in the mature and old tooth extraction groups compared with their age-matched controls, but there was no significant difference in the CA1-region or dentate gyrus between the mature or old tooth extraction groups and their age-matched controls. In young mice, there was no significant difference in the number of neurons in CA1, CA3, or dentate gyrus region between the tooth extraction and control groups. The findings indicated that tooth extraction after tooth eruption enhances the effects of aging on the hippocampus in mice. exposed to chronic stress 7) , tooth loss is thought to act as a chronic stressor. Chronic stress impairs spatial memory 8) , and leads to a decrease in neurons 9) , an increase in glial fibrillary acidic protein-positive cells 10) , a decrease in acetylcholine release in the higher centers of the brain 11) , particularly the hippocampus, and a decrease in Fos-positive cells in areas of the hippocampus considered important for learning 12). In all of these studies, however, the teeth were extracted at young, mature, and old ages and soon induces functional and morphologic changes. In the present study, we extracted the teeth soon after eruption, maintained the animals until maturation

The effects of early tooth extractions on age-associated changes in cognitive function were evaluated. Specifically, teeth were extracted at an early age in senescence-accelerated mice (SAM)P8, and the number of glial fibrillary acid protein (GFAP)-positive astrocytes and spatial perception were evaluated at young, mature, and old ages. The following results were obtained: 1. Concerning spatial perception evaluated by the Morris water maze test, the shortening of the time until the animals reached the platform was significantly slower in mature or old mice of the tooth extraction group compared with age-matched controls. However, no significant difference was noted in the rate of shortening in young mice between the tooth extraction and control groups. 2. The number of GFAP-positive cells was significantly higher in the CA3 region of the hippocampus in the mature or old mice of the tooth extraction group compared with age-matched controls. However, no significant difference was observed in the CA1 and dentate gyrus (DG) region of the hippocampus in the mature or old mice and in the CA1, CA3, and DG region in the young mice between the two groups. These results suggest that the loss of teeth at an early age accelerated aging and that GFAP-positive astrocytes increased to compensate for a decrease in pyramidal cells. acetylcholine release 3) , and number of c-Fos proteinpositive cells linked to learning tests 8) have been reported. In addition, astrocytes positive for glial fibrillary acid protein (GFAP), which is produced as an intermediate filament protein, have been reported to show a compensatory increase with a decrease in pyramidal cells and to be an index of aging 9-11). However, these findings have been obtained by extracted teeth at young, mature, or old ages to evaluate its effects after extractions soon. In this study, therefore, we extracted teeth from young senescenceaccelerated mice (SAM)P8 shortly after eruption, maintained the animals until mature or old ages, and examined whether the long-term absence of teeth induces functional and morphological changes in the