Masafumi Fujita

Mapping Brain Region Activity during Chewing: A Functional Magnetic Resonance Imaging Study

Mastication has been suggested to increase neuronal activities in various regions of the human brain. However, because of technical difficulties, the fine anatomical and physiological regions linked to mastication have not been fully elucidated. Using functional magnetic resonance imaging during cycles of rhythmic gum-chewing and no chewing, we therefore examined the interaction between chewing and brain regional activity in 17 subjects (aged 20-31 years). In all subjects, chewing resulted in a bilateral increase in blood oxygenation level-dependent (BOLD) signals in the sensorimotor cortex, supplementary motor area, insula, thalamus, and cerebellum. In addition, in the first three regions, chewing of moderately hard gum produced stronger BOLD signals than the chewing of hard gum. However, the signal was higher in the cerebellum and not significant in the thalamus, respectively. These results suggest that chewing causes regional increases in brain neuronal activities which are related to biting force.

Age-related Changes in Brain Regional Activity during Chewing: A Functional Magnetic Resonance Imaging Study:

Age-related changes in mastication-induced brain neuronal activity have been suggested. However, in humans, little is known about the anatomical regions involved. Using fMRI during cycles of rhythmic gum-chewing and no chewing, we have examined the effect of aging on brain regional activity during chewing in young adult (19–26 yrs), middle-aged (42–55 yrs), and aged (65–73 yrs) healthy humans. In all subjects, chewing resulted in a bilateral increase in the BOLD signals in the sensorimotor cortex, cerebellum, thalamus, supplementary motor area, and insula, and a unilateral increase in the right prefrontal area. In the first three regions, the signal increases were attenuated in an age-dependent manner, whereas, in the right prefrontal area, the converse was seen. The remaining two regions showed no significant differences with ages. These results indicate that chewing causes regional increases in neuronal activity in the brain, some of which are age-dependent.

The molarless condition in aged SAMP8 mice attenuates hippocampal Fos induction linked to water maze performance

The involvement of dysfunctional teeth in senile hippocampal activity was evaluated by examining, in aged SAMP8 mice, the effect of cutting off the upper molars (molarless condition) on hippocampal induction of the protein product, Fos, of the immediate early gene, c-fos, and on spatial performance in a water maze. The molarless condition caused a reduction in the number of Fos-positive cells in the hippocampal CA1 region, in which Fos immunoreactivity was localized in the cell nuclei. This effect was more pronounced the longer the molarless condition persisted. The suppression of both learning ability and Fos induction in the CA1 induced by the molarless condition was considerably reduced by restoring the lost molars with artificial crowns. Taken together with the plethora of research showing a relationship between stress, aging and hippocampal function and our past findings [Brain Res. 1999; 826: 148-53; Behav. Brain Res. 2000;108: 145-55; Exp. Gerontol. 2001; 36:283-95], the present results suggest the detrimental effects of a reduction in chewing on hippocampal processing in aged SAMP8 mice that would be linked with stress induced by the molarless condition.

Evidence for involvement of glucocorticoid response in the hippocampal changes in aged molarless SAMP8 mice

The involvement of glucocorticoid response in the hippocampal changes in aged SAMP8 mice after removal of their upper molar teeth (molarless condition) was examined using biochemical, morphological and behavioral techniques. Molarless mice showed plasma corticosterone levels to be significantly greater than those in molar-intact control mice. Pretreatment with metyrapone, which suppresses the stress-induced rise in plasma corticosterone levels, prevented the molarless condition-induced increase in plasma corticosterone levels, reduction in CA1 pyramidal neuron numbers, and impairment of spatial learning. The results suggest a link between the molarless condition and the glucocorticoid response, which may be involved in spatial learning deficits and hippocampal neuronal death in aged SAMP8 mice.

Changes in the septohippocampal cholinergic system following removal of molar teeth in the aged SAMP8 mouse.

We investigated the effect of dysfunctional teeth on age-related changes in the septohippocampal cholinergic system by assessing acetylcholine (ACh) release and choline acetyltransferase (ChAT) activity in the hippocampus and ChAT immunohistochemistry in the medial septal nucleus and the vertical limb of the diagonal band in young-adult and aged SAMP8 mice after removal of their upper molar teeth (molarless condition). Aged molarless mice showed decreased ACh release and ChAT activity in the hippocampus and a reduced number of ChAT-immunopositive neurons in the medial septal nucleus compared to age-matched control mice, whereas these effects were not seen in young-adult mice. The results suggest that the molarless condition in aged SAMP8 mice may enhance an age-related decline in the septohippocampal cholinergic system.

Evidence for involvement of dysfunctional teeth in the senile process in the hippocampus of SAMP8 mice

In order to evaluate the involvement of dysfunctional teeth in age-related deficits in hippocampal function, we examined the effect of removal of molar teeth (molarless condition) on neuronal degeneration and glial fibrous acidic protein (GFAP) expression in the hippocampus and on learning ability in a water maze test in young, middle-aged, and aged accelerated senescence-prone mice (SAMP8). The molarless condition enhanced an age-dependent decrease in both learning ability and the number of neurons in the hippocampal CA1 subfield and the age-dependent increase in the number and hypertrophy of GFAP-labeled astrocytes in the same subfield. These observations suggest that the molarless condition may be involved in the senile process in the hippocampus in SAMP8 mice.

Molarless-induced changes of spines in hippocampal region of SAMP8 mice.

We examined the effect of the molarless condition on the dendritic spines of hippocampal pyramidal cells in SAMP8 mice in comparison to its effect on learning ability in a maze test. The molarless condition caused a decrease in the number of the spines of CA1 pyramidal cells only in the aged mice showing a reduced learning ability. The results suggest the involvement of the molarless condition in an attenuation of input activities in the hippocampal synapses.

Topography of commissural fibers in the corpus callosum of the cat: a study using WGA-HRP method

The topography of the commissural fibers in the corpus callosum (CC) of the cat was systematically investigated using the WGA-HRP method. WGA-HRP was injected into various parts of the cerebral cortex and locations of WGA-HRP-stained commissural fibers in the CC were examined. Commissural fibers were arranged in a topological fashion in the CC. Cortical areas rostral to the cruciate sulcus (CrS), corresponding to motor or premotor cortices, projected fibers into the genu of the CC, while fibers from the cortex caudal to the CrS passed through the CC slightly caudal to the genu. When WGA-HRP was injected into the lateral gyrus (LG), it was observed that fibers from the anterior LG passed through the anterior one-third of the CC, whereas those from the posterior LG passed through or near the splenium, and fibers from the middle LG passed between those from the anterior and posterior LG. Similarly, the suprasylvian gyrus (SSG) projected commissural fibers in the CC in a rostrocaudal topological manner. Fibers from the anterior SSG passed through the anterior one-third of the CC, and those from the middle SSG through the middle one-third of the CC and upper part of the splenium. Injection into the most posterior part of the middle SSG revealed fibers passing through the caudal end of the splenium. Callosal fibers from the anterior SSG were focused on in this study, because this area (area 2v) is considered one of the vestibular projection cortices and is an area of special interest to the authors. Callosal fibers from the anterior SSG were observed to pass through the anterior one-third of the body of the CC. When WGA-HRP was injected into auditory areas, fibers from the anterior and middle ectosylvian gyri (ESG) were observed to pass through the posterior one-third of the body of the CC or through the splenium, while fibers from the posterior ESG passed through the splenium. WGA-HRP was also injected into the cingulate gyrus (CiG). Fibers from the anterior CiG (area 24) passed through the anterior portion of the CC while those from the posterior CiG (area 23) passed through the posterior portion of the CC.

Effect of unpleasant loud noise on hippocampal activities during picture encoding: an fMRI study.

The functional link between the amygdala and hippocampus in humans has not been well documented. We examined the effect of unpleasant loud noise on hippocampal and amygdaloid activities during picture encoding by means of fMRI, and on the correct response in humans. The noise reduced activity in the hippocampus during picture encoding, decreased the correct response and increased the activity of the amygdala. A path diagram using structural equation modeling suggested that hippocampus activity might be depressed by high amygdala activity. Therefore, noise should diminish memory by reducing hippocampal activity, which might be depressed by high amygdala activity.