Shinjiro Miyake

CHEWING AMELIORATES STRESS-INDUCED SUPPRESSION OF HIPPOCAMPAL LONG-TERM POTENTIATION

Research has established that severe stress adversely affects hippocampal memory, and chewing has been suggested to restore impaired cognitive functions in the hippocampus. To address how chewing involves stress-attenuated hippocampal memory process, we measured the long-term potentiation (LTP) of hippocampal slices of adult male rats that had experienced restraint stress, including some rats that were allowed to chew a wooden stick during the stress period and other rats that were not. The three experimental conditions were: 1) restraint stress without chewing (ST), 2) restraint stress with chewing (SC), and 3) no treatment (CT). We prepared hippocampal slices and collected trunk blood from all experimental animals. For rats in the two stressed groups, we collected tissue and blood at one of three post-stress time points: immediately after, 24 h after, or 48 h after exposure to the stressor. We found that the magnitude of LTP in both group ST and SC was significantly attenuated immediately after stress exposure. However, within 24 h after the end of the stress period, LTP had returned to the control level in group SC whereas it remained low in group ST. At the same post-stress time point, we found that facilitation of N-methyl-D-aspartate (NMDA) receptors by bath-applied glycine had less effect on the magnitude of LTP in group SC than on group ST, suggesting that most NMDA receptors had already become functionally restored in group SC by that time. Plasma concentration of adrenocorticotropic hormone was significantly elevated only in group ST immediately after exposure to the stressor, reflecting the involvement of chewing in decreasing subsequent corticosterone secretion. Thus, the present study demonstrates that chewing ameliorates the stress-induced impairment of NMDA receptor-mediated LTP, suggesting chewing as a good strategy to cope with severe stress by suppressing excessive endocrine responses.

Effects of Mandibular Deviation on Brain Activation During Clenching: An fMRI Preliminary Study

Abstract Using functional magnetic resonance imaging (fMRI) in eight healthy human subjects, the present study measured blood oxygenation level-dependent (BOLD) signals during clenching in a malocclusion model, using a custom-made splint that forced the mandible to a retrusive position and a splint of no modification for control, and compared the results to the BOLD signals during the corresponding resting conditions. An individual visual analog scale (VAS) score was also examined during clenching to evaluate the interactions between fMRI data and psychiatric changes. During both clenchings, activations in four brain regions (premotor cortex, prefrontal cortex, sensorimotor cortex, and insula) were seen. However, clenching in the malocclusion model, with psychological discomfort, increased additionally BOLD signals in the anterior cingulate cortex and the amygdala. Furthermore, there was a parallel relationship between BOLD signal intensities and VAS scores in these two regions. The findings may suggest the involvement of clenching with malocclusal conditions in the emotion and/or pain-related neural processing in the brain.

Biting reduces acute stress-induced oxidative stress in the rat hypothalamus.

Abstract We investigated the inhibitory effect of para-masticatory activity, namely biting, on restraint stress-induced oxidative stress. A blood brain barrier-permeable nitroxyl spin probe, 3-methoxycarbonyl-2,2,5,5,-tetramethylpyrrolidine-1-oxyl (MC-PROXYL), was administered to rats and L-band electron spin resonance (ESR) and ESR-computerized tomography (ESR-CT) imaging were used to show that the decay rate constant of MC-PROXYL in the hypothalamus of isolated brain after 30 min of restraint stress was more rapid than in unrestrained control rats, suggesting that restraint was associated with oxidative stress. Interestingly, biting during restraint stress caused the decay rate constant of MC-PROXYL in isolated brain to approach that of the control group. These observations suggest that biting suppresses oxidative stress induced by restraint stress, and that the anti-stress effect of masticatory motor activity movements, such as biting, are important for reducing the adverse effects associated with exposure to psychological stressors.

Chewing rescues stress-suppressed hippocampal long-term potentiation via activation of histamine H1 receptor

We have previously found in rats that chewing, an active behavioral strategy to cope with a stressful situation, rescues long-term potentiation (LTP) in the hippocampus through activating stress-suppressed N-methyl-D-aspartate (NMDA) receptor function. To further examine the mechanisms underlying this ameliorative effect of chewing, we studied the involvement of the histaminergic system, which has been shown to be activated by mastication, in the LTP of hippocampal slices of rats that were allowed to chew a wooden stick during exposure to immobilization stress. Chewing failed to rescue stress-suppressed LTP in the rats treated with histamine H1 receptor (H1R) antagonist pyrilamine (5 mg/kg, i.p.) before exposure to stress, although administration of pyrilamine did not affect LTP in naive rats and in stressed rats that did not chew. However, when pyrilamine was administrated immediately after exposure to stress, chewing rescued LTP whose magnitude was statistically comparable to that in the rats that chewed without drug treatment. These results suggest that chewing-induced histamine release in the hippocampus and the subsequent H1 receptor activation may be essential to rescue stress-suppressed synaptic plasticity.

Nitric oxide levels in rat hypothalamus are increased by restraint stress and decreased by biting

Abstract Mastication, which includes biting, is of great importance not only for the intake of food but also for the mental, physical and physiological functioning of the body. For example, biting suppresses the stress response. Although biting and nitric oxide (NO) appear to modulate brain dynamics during stress, the underlying mechanisms have not been elucidated. In this study, we examined the effect of biting during restraint stress on NO levels in the rat hypothalamus. To this end, we used NO-selective electrodes that were calibrated by electron spin resonance (ESR) spectroscopy. We implanted the electrodes and probes for perfusion of solutions into the brain of rats, near the hypothalamus. Saline containing 10 mM N-nitro-L-arginine methyl ester (L-NAME), which is one of the most commonly used inhibitors of nitric oxide synthase (NOS), was employed as the perfusate. L-NAME prevented increases in NO levels in the rat hypothalamus that were induced by restraint stress and biting. Hypothalamic NO levels in rats under restraint stress for 180 min were increased above levels observed in unrestrained control rats. The increase in hypothalamic NO (from 2.123 μM to 4.760 μM) during restraint stress was reduced after biting for 30 min. The decay rate of NO levels after biting was −0.584 pA/min (−0.071 μM/min). We conclude that: (i) it is possible to evaluate NO levels in vivo in rat brain; (ii) NO levels are increased by restraint stress; and (iii) this increase is prevented by biting behavior.

Chewing ameliorates stress-induced suppression of spatial memory by increasing glucocorticoid receptor expression in the hippocampus.

Chewing alters hypothalamic-pituitary-adrenal axis function and improves the ability to cope with stress in rodents. Given that stress negatively influences hippocampus-dependent learning and memory, we aimed to elucidate whether masticatory movements, namely chewing, improve the stress-induced impairment of spatial memory in conjunction with increased hippocampal glucocorticoid receptor expression. Male Sprague-Dawley rats were subjected to restraint stress by immobilization for 2h: the stress with chewing (SC) group were allowed to chew on a wooden stick during the latter half of the immobilization period, whereas the stress without chewing (ST) group were not allowed to do so. Performance in the Morris water maze test was significantly impaired in the ST group compared with the SC group. Further, the numbers of glucocorticoid receptor immunopositive neurons in the hippocampal cornu ammonis 1 region were significantly lower in the ST group than in the control and SC groups. The control and SC rats showed no significant differences in both the water maze performance and the numbers of glucocorticoid receptor-immunopositive neurons. The immunohistochemical finding correlated with the performance in the water maze test. These results suggest that chewing is a behavioral mechanism to cope with stress by increasing hippocampal glucocorticoid receptor expression.

Stress and chewing affect blood flow and oxygen levels in the rat brain

OBJECTIVE Mastication, including chewing, would be of great importance not only for food intake, but also for the mental, physical and physiological functioning of the body. Our study showed that mastication, especially chewing, suppresses the stress response and was regarded as a biological response to defend against various stresses. Although mastication altered brain function during stress, the underlying mechanisms have not been elucidated. METHODS The effects of chewing during restraint stress on blood flow and oxygen partial pressure (PO(2)) levels in the rat amygdala and hypothalamus were measured using laser Doppler flowmetry and O(2)-selective electrodes. RESULTS Amygdaloidal and hypothalamic blood flow were not affected by restraint stress, but PO(2) levels were significantly reduced by restraint stress for 180 min compared to unrestrained control rats. The decrease in amygdaloidal and hypothalamic PO(2) levels during restraint stress was reduced after chewing for 30 min. CONCLUSION These results suggested that it is possible to evaluate hypothalamic and amygdaloidal blood flow and PO(2) levels in rat brains during restraint stress. Restraint stress reduced cerebral PO(2) levels. In addition, chewing would lead to increased blood flow and to recover cerebral PO(2) levels.

Combination of chewing and stress up-regulates hippocampal glucocorticoid receptor in contrast to the increase of mineralocorticoid receptor under stress only

In general, acute immobilization stress increases plasma corticosterone levels that signal the hypothalamic-pituitary-adrenal axis. Mineralocorticoid receptors and glucocorticoid receptors in the hippocampus perform crucial roles in this feedback mechanism. In the present study, we investigated the effects of chewing under stress on the rat hippocampal mineralocorticoid and glucocorticoid receptors by immunohistochemistry. We separated rats into a control group, a 2-h immobilization stress group (stress only group), and a 2-h immobilization stress group that was allowed to chew on a wooden stick for the latter 1h (stress with chewing group). Mineralocorticoid receptor immunoreactive cells with nucleus staining in the hippocampal CA1 area were scattered in the pyramidal cell layer. The stress only group showed the densest distribution of immunoreactive cells; however, the density of the immunoreactive cells in the stress with chewing group was similar to that of the control group. Changes in immunoreactive cell density were not visible in other areas of the hippocampus, namely, the CA3 area and dentate gyrus. Image analysis indicated that the increase in the mineralocorticoid receptor immunoreactive area within a fixed area in the stress only group was statistically significant compared with those in the control group and the stress with chewing group. On the other hand, glucocorticoid receptor immunoreactive cells in the CA1 area seemed to be increased in the stress with chewing group, but not in the stress only group. Image analysis indicated that this increase was statistically significant. These results suggest that immobilization and immobilization with chewing differentially affect these two types of glucocorticoid receptors in the rat hippocampus. Considering that chewing has alleviative effects against stress, glucocorticoid receptor elevation in the hippocampal CA1 area is one of the neuronal mechanisms of coping with stress.

Bruxism and Stress Relief

The masticatory organ, originally developed as a branchial system, has evolved over a long period of geological time through a stage in which it was predominantly a tool for expressing aggression into an organ for emotional management. In humans, the strong grinding and clenching function of the masticatory muscles, known as bruxism, plays a role in mitigating stress-induced psychosomatic disorders by down-regulating the limbic system, the autonomic nervous system, and the hypothalamic-pituitary-adrenal (HPA) axis. Experimental research results showed that bruxism-like activity (BLA) has beneficial effects on stress-induced reactions, such as increased expression of Fos, neuronal nitric oxide synthase (nNOS), dual phosphorylated extracellular signal-regulated kinase (pERK1/2), corticotropin-releasing factor (CRF), and free radicals in the paraventricular nucleus (PVN) of the hypothalamus. It has also been shown to cause alterations in the blood neutrophil/lymphocyte ratio, adrenocorticotropic hormone (ACTH) level, and stomach ulcer formation in animals studies and has increased amygdala neuronal activity and salivary chromogranin A level in human studies. These findings strongly suggested that parafunctional activity of the masticatory organ—aggressive BLA behavior—has the ability to decrease stress-induced allostatic overload. The health of the masticatory organ depends critically on occlusion, which must be of sufficient quality to carry out its important role in managing stress successfully. Occlusion and the brain must function in harmony. For these reasons, we must integrate the study of occlusion into the broader scope of medical science; in so doing, we can meaningfully advance the state of the art of dental care and general health care.

Mechanical properties of orthodontic wires covered with a polyether ether ketone tube

OBJECTIVES To evaluate the esthetics and frictional force of an orthodontic wire passed through a newly designed tube made of a polyether ether ketone (PEEK) resin. MATERIALS AND METHODS Two types of standard PEEK tubes were prepared at 0.5 × 0.6ф and 0.8 × 0.9ф, and different archwires were passed through the tubes. Color values were determined according to brightness and hues. Friction was assessed with different bracket-wire combinations, and surface roughness was determined by stereomicroscopy before and after the application of friction. RESULTS The PEEK tube showed a color difference that was almost identical to that of coated wires conventionally used in clinical practice, indicating a sufficient esthetic property. The result of the friction test showed that the frictional force was greatly reduced by passing the archwire through the PEEK tube in almost all of the archwires tested. CONCLUSIONS Use of the new PEEK tube demonstrated a good combination of esthetic and functional properties for use in orthodontic appliances.