Relationship between light and dark period activity cycles and oral condition in senescence-accelerated mice.

We investigated the effect of tooth absence and masticatory abnormalities due to powdered food feeding starting during the juvenile period on light and dark period activity cycles in senescence-accelerated mice (SAMP1). SAMP1 were divided into 5 groups: Group 1, maxillo-mandibular molar tooth extraction; Group 2, maxillary molar tooth extraction; Group 3, mandibular molar tooth extraction; Group 4, powdered food; and Group 5, sham-operated control. Senescence was observed earliest in the powdered food group. Total 24-hour activity was higher in the control group than in the four other groups. In the powdered food group, the dark period activity decreased to less than 60% of the total activity in the 36th week. In the tooth extraction groups (Groups 1-3), dark period activity decreased to less than 60% of the total activity in the 40th week. The control group dark period activity remained above 60% for the entire experimental period. Thus, the distinction between the light and dark periods disappeared earlier in the four experimental groups compared with the control group. Significant correlations were noted among total activity, degree of senescence, and percent dark period activity in each experimental group. Functional masticatory insufficiency promoted dementia and behavioral abnormalities in SAMP1.

Masticatory function and cognitive function.

Recent studies have suggest that masticatory (chewing) function is useful for maintaining neurocognitive function in the elderly. For example, a reduced ability to masticate, such as that resulting from toothlessness or soft-diet feeding, causes learning and memory deficits in aged animals and pathologic changes in the hippocampus. In addition, occlusal disharmony impairs hippocampal memory processes via chronic stress, and induces similar hippocampal pathology. Chewing, however, rescues stress-induced suppression of long-term potentiation in the hippocampus and the stress-induced impairment of hippocampal-dependent learning. These findings strongly suggest a link between mastication and neurocognitive function.

Malocclusion induces chronic stress.

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.

The bite-raised condition enhances the aging process in the dorsal and ventral hippocampus.

The bite raised condition decreases the number of neurons and increases the amount of glial fibrillary acidic protein in the hippocampus of aged SAMP8 mice. In the present study, we examined whether these effects differ between the dorsal and ventral hippocampus. In bite-raised SAMP8 mice, the number of neurons was significantly lower in the hippocampal CA1 and dentate gyrus (DG) subfields compared to control mice. In the bite raised condition, the number of neurons was significantly lower in both the dorsal and ventral CA3 subfields, and the number of glial fibrillary acidic protein-labeled astrocytes was increased in the CA1, CA3, and DG subfields, compared to control mice. These data suggest that in aged SAMP8 mice, the bite-raised condition enhanced aging processes in both the dorsal and ventral hippocampus.

The bite-raised condition in aged SAMP8 mice reduces the expression of glucocorticoid receptors in the dorsal and ventral hippocampus.

In the present study, we examined whether the effects induced by the bite-raised condition on glucocorticoid receptor (GR) expression differ between the dorsal and ventral hippocampus in SAMP8 mice. In the bite-raised condition, the number of GR-immunoreactive cells was significantly decreased in both the dorsal and ventral CA1 and dentate gyrus (DG) subfields of the hippocampus compared to control mice, as revealed by immunohistochemical analysis. The decrease in the number of GR-immunoreactive cells tended to be greater in the dorsal hippocampus than in the ventral hippocampus. Only in the DG subfield was there a significant difference in the number of GR-immunoreactive cells between the dorsal and ventral hippocampus. These findings suggest that in aged SAMP8 mice, the bite-raised condition decreases the number of GR-immunoreactive cells in both the dorsal and ventral hippocampus.

Occlusal disharmony attenuates glucocorticoid negative feedback in aged SAMP8 mice.

To evaluate the mechanism underlying impaired cognitive function due to occlusal disharmony, we examined the effect of the bite-raised condition on spatial performance and hippocampal expression of glucocorticoid receptors (GR) and glucocorticoid receptor messenger ribonucleic acid (GRmRNA) using behavioral, immunohistochemical, and in situ hybridization techniques. Learning ability in the water maze test was significantly impaired in aged bite-raised mice compared with age-matched control mice. There was no difference between control and bite-raised young and middle-aged mice. Also, immunohistochemical and in situ hybridization analysis showed that the bite-raised condition enhanced the age-related decrease in GR and GRmRNA expression in the hippocampus. In particular, GR and GRmRNA expressions were significantly decreased in aged bite-raised mice compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice decreases GR and GRmRNA, which impairs the hypothalamic-pituitary-adrenal feedback inhibition, thereby leading to memory deficits.

Duration-dependent effects of the bite-raised condition on hippocampal function in SAMP8 mice.

We evaluated the effect of the duration of occlusal disharmony induced chronic stress on hippocampal function by examining spatial memory in the Morris water maze and on the number of hippocampal neurons in aged senescence-accelerated prone (SAMP8) mice. The bite of SAMP8 mice was raised 0.1 mm using dental adhesive. Groups of mice were tested in the Morris water maze 8, 11, or 22 d after raising the bite. The results indicated that the longer the duration of the bite-raised condition, the greater the impairment in spatial learning ability and the greater the decrease in the number of neurons in the hippocampal CA3 subfield. Thus, behavioral and morphologic deficits induced by the bite-raised condition in aged SAMP8 mice are influenced by the duration of the occlusal disharmony.