Both the ventromedial hypothalamus (VMH) and the mesencephalic trigeminal sensory nucleus (Me5) are densely innervated by histaminergic neurons. The depletion of neuronal histamine (HA) from the Me5 by the bilateral microinfusion of a-fluoromethylhistidine (FMH) reduced the eating speed and prolonged meal duration, while leaving meal size unaffected. HA depletion from the VMH increased the size of the meal and prolonged its duration, but not the eating speed. HA turnover rate increased in the region including Me5 and hypothalamus by mastication. The HA function activated by mastication began earlier in the Me5 and later in the hypothalamus due to a signal originating from the oral proprioceptors and initiated by chewing. Neuronal histamine activated by mastication not only suppressed food intake via H1 receptor in the VMH and paraventricular nucleus (PVN), but also increased lipolysis and suppressed lipogenesis in peripheral adipose tissue via sympathetic nerves. Mastication is applied clinically for weight reduction with use of mastication chart.

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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.

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[in Japanese]

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The purpose of this study was to evaluate whether it is possible to objectively determine the habitual chewing side in complete denture wearers, by observing the dentition side to which food samples placed on the mid-line of the dorsum of the tongue were transported by the tongue at the beginning of mastication. The subjects were 15 patients wearing complete dentures over an average of 7 years. First, the masticatory performance on the bilateral dentition sides in the subjects was investigated using a sieve to examine the size of masticated food. After placing an approximately 2 mm gelatin specimen on the mid-line of the dorsum of the tongue in the subjects, the dentition sides to which the specimen was transported by the tongue were observed. Furthermore, after placing cotton roll, the same observation was performed.

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Unohana agar gel, Hijikini agar gel, Kombumame agar gel were prepared in order to investigate effect of those additives on physical properties of agar gels in terms of rupture properties. The taste of young and aged panels for those food mixed agar gels was evaluated by sensory test. Rupture strain, stress and energy decreased while modulus of elasticity increased after mixing those foods in agar gels. The result of sensory test indicated that the food mixed agar gels were easy to be swallowed but poor in flavor and taste for the young panel. On the other hand, Kombumame agar gel was easy to be swallowed and good in flavor and taste for the aged panel with masticating difficulties.

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As the functions of chewing gum, improvement of masticatory ability, acceleration of cerebral blood flow, actions on the central nervous system, promotion of saliva secretion and other direct effects of mastication are recognized. As the regulation mechanism of appetite, the satiety center and feeding center regulate eating actions. There are few studies about the effects of mastication on these centers, in particular, few clinical studies. It was proved by Zucker's rat experiments of genic obese animals that secretion of histamine among food-intake control substances depends on mastication, namely on the stimulus by chewing. Based on these backgrounds, effects of mastication on insulin secretion by masticating chewing gum before meal were examined.
Nineteen healthy women from 19 to 25 year old were subjected to a 75g-glucose tolerance test after chewing a gum base for 15 minutes. Before gum mastication, 3, 6, 9 and 15 minutes after the mastication, and succeedingly 15, 30, 60 and 120 minutes after the 75g-glucose tolerance, that is 9 times in total, blood was gathered from a vein, and blood sugar and insulin were measured. Furthermore, similar measurements were performed for the case where gum was not masticated.
As a result, the case where the gum base was masticated showed more insulin secretion than the control in the 30-minute value after the 75g-glucose tolerance. From these results, the effects of mastication on the centers were suggested.

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As the regulation mechanism of appetite, the satiety center and feeding center regulate eating actions. There are few studies about the effects of mastication on these centers, in particular, few clinical studies. It was proved by Zucker's rat experiments of genic obese animals that secretion of histamine among food-intake control substances depends on mastication, namely on the stimulus by chewing. On the other hand, our previous report suggested the effects of mastication on the centers. Based on these backgrounds, effects of mastication on insulin secretion by masticating chewing gum before meal were examined.
Nineteen healthy women from 19 to 25 year old were subjected to a 75g-glucose tolerance test after chewing a sugar-containing gum for 15 minutes. Before gum mastication, 3, 6, 9 and 15 minutes after the mastication, and succeedingly 15, 30, 60 and 120 minutes after the 75g-glucose tolerance, that is 9 times in total, blood was gathered from a vein, and blood sugar and insulin were measured. Furthermore, similar measurements were performed for the case where sugar liquid of the same quantity as sugar-containing gum.
As a result, in the 30-minute value after the 75g-glucose tolerance the case where the sugarcontaining gum was masticated showed less insulin secretion than the case where the sugar liquid was taken in. On the other hand, the case where the sugar-containing gum was masticated showed lower total-insulin secretion than the case where the sugar liquid was taken in. From these results, the effects of mastication on the centers are suggested, and it can be concluded that mastication contributes to the acceleration of sugar metabolism. And, one can expect by gum mastication similar effects as a low-insulin diet.

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