Yukiko Ichihashi

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.

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.

Effects of early tooth loss on the hippocampus in senescence-accelerated mice

Abstract 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.

Early toothless condition suppresses cell proliferation in the hippocampal dentate gyrus of SAMP8 mice

Early toothlessness in senescence-accelerated prone (SAMP8) mice leads to increased plasma corticosterone levels, learning deficits, neuronal death, and increased astroglial responsiveness in the hippocampus. New cells are generated in the hippocampal dentate gyrus (DG) throughout life in animals as well as humans. Neurogenesis in the hippocampal DG is sensitive to glucocorticoid levels and environmental triggers such as learning. Here we investigated the mechanisms underlying impaired hippocampal function resulting from early masticatory dysfunction, by examining the effects of tooth loss soon after tooth eruption on plasma corticosterone levels, learning ability in the Morris water maze test, and cell proliferation in the hippocampal DG of 1-, 5-, and 9-mo-old SAMP8 mice. Bromodeoxyuridine, a marker of newborn cells, was injected, and BrdU-positive cells were quantitatively analyzed to detect cell proliferation in the hippocampal DG using immunohistochemical techniques. Early toothlessness enhanced the age-related increase in plasma corticosterone levels and learning deficits, and led to a decrease in the number of BrdU-positive cells in the hippocampal DG. Plasma corticosterone levels, learning deficits, and the number of BrdU-positive cells in the hippocampal DG was significantly different between in 5- and 9-mo-old early toothless mice and age-matched control mice, but not between 1-mo-old early toothless mice and controls. These findings suggest that early toothlessness leads to increased plasma corticosterone levels and a decrease in cell proliferation in the hippocampal DG, thereby leading to learning deficits.

Effects of early tooth extractions on hippocampal GFAP-positive cells in aged senescence-accelerated mice

Abstract 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.

Effects of occlusal disharmony during pregnancy on maze performance and hippocampal dentate gyrus cell proliferation in adult progeny

SC. Chewing significantly counteracted the stress-reduced number of the open-arm entries into the maze (2.9 ± 0.8 and 7.6 ± 0.8 times in ST and SC, respectively; n = 8 each; p < 0.01) to a level comparable to the control (4.2 ± 0.8 times; n = 9; p = 0.08). The extracellular concentration of dopamine, but not noradrenaline and serotonin, in the ventral hippocampus of the rats in SC was significantly higher than those in ST at the same post-stress time period (168 ± 15% and 250 ± 11% of baseline in ST and SC, respectively; n = 8 each; p < 0.01). The number of open-arm entries in ST and SC became comparable by administrating SCH23390 (1.9 ± 0.8 and 1.8 ± 0.5 times in ST and SC with drug treatment, respectively; n = 8 each; p = 0.89). Our results suggest that chewing activates the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiety-like behavior.

Long-lasting toothless condition progresses aging processes in the hippocampus

In order to assess whether toothless (extracting the upper molar teeth) at an early period after eruption of teeth (early toothless) exerts greater effects on hippocampal aging processes than late toothless, morphological and behavioral studies were done in the SAMP8 mice. Not only early toothless enhanced age-dependent decline in learning ability in a water maze test, but also in more decreased the number of hippocampal neurons than those in the age-matched control condition. However, the effects of late toothless was not significant, when compared with those in the control condition. The data suggest that a long-lasting toothless condition may result in progressing aging processes in the hippocampus.