Search

We assessed the effects of chewing behavior on the lung-metastasis-promoting impact of chronic psychological-stress in mice. Human breast-cancer cells (MDA-MB-231) were injected into the tail vein of female nude mice. Mice were randomly divided into stress, stress-with-chewing, and control groups. We created chronic stress by placing mice in small transparent tubes for 45 min, 3 times a day for 7 weeks. Mice in the stress-with-chewing group were allowed to chew wooden sticks during the experimental period. The histopathological examination showed that chronic psychological-stress increased lung metastasis, and chewing behavior attenuated the stress-related lung metastasis of breast-cancer cells. Chewing behavior decreased the elevated level of the serum corticosterone, normalized the increased expression of glucocorticoid, and attenuated the elevated expression of adrenergic receptors in lung tissues. We also found that chewing behavior normalized the elevated expression of inducible nitric oxide synthase, 4-hydroxynonenal, and superoxide dismutase 2 in lung tissues, induced by chronic stress. The present study demonstrated that chewing behavior could attenuate the promoting effects of chronic psychological-stress on the lung metastasis of breast-cancer cells, by regulating stress hormones and their receptors, and the downstream signaling-molecules, involving angiogenesis and oxidative stress.

Sarcopenia is a complication of Chronic Obstructive Pulmonary Disease (COPD) that negatively affects physical activity and quality of life. However, the underlying mechanism by which COPD affects skeletal muscles remains to be elucidated. Therefore, we investigated the association between oxidative stress and structural alterations in muscles in elastase-induced emphysema mouse models.Twelve-week-old male C57BL/6J mice were treated with either intratracheal porcine pancreatic elastase (PPE) dissolved in saline, or saline alone. The mice were euthanized 12 weeks after treatment, and the lungs and limb muscles were used for protein analysis of oxidative stress, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and muscle atrophy signaling pathway related with oxidative stress. Furthermore, C57BL/6J mice treated with PPE or saline were analyzed for the effects of oral administration of astaxanthin or p38 inhibitor.The weight of the soleus muscle, proportion of type I muscle fibers, and cross-sectional areas of muscle fibers in the PPE group were lower than those in the control group. Oxidative stress marker levels in the PPE group were elevated in skeletal muscles. The p38 MAPK signaling pathway was activated in the soleus muscles, leading to the activation of the ubiquitin-proteasome system and autophagy. Astaxanthin and p38 inhibitors attenuated alterations in muscle structure through the deactivation of the p38 MAPK signaling pathway.This study provides first evidence in COPD mouse model that oxidative stress trigger a series of muscle structural changes. Our findings suggest a novel target for sarcopenia in COPD.

Long-term tooth loss is associated with the suppression of hippocampal neurogenesis and impairment of hippocampus-dependent cognition with aging. The morphologic basis of the hippocampal alterations, however, remains unclear. In the present study, we investigated whether tooth loss early in life affects the hippocampal ultrastructure in senescence-accelerated mouse prone 8 (SAMP8) mice, using transmission electron microscopy. Male SAMP8 mice were randomized into control or tooth-loss groups. All maxillary molar teeth were removed at 1 month of age. Hippocampal morphologic alterations were evaluated at 9 months of age. Tooth loss early in life induced mitochondrial damage and lipofuscin accumulation in the hippocampal neurons. A thinner myelin sheath and decreased postsynaptic density length were also observed. Our results revealed that tooth loss early in life may lead to hippocampal ultrastructure remodeling and subsequent hippocampus-dependent cognitive impairment in SAMP8 mice with aging.

Wnt signaling is relevant for a wide range of biological processes, including reproductive function. The function of Wnt10a in female fertility, however, remains obscure. In the present study, we explored the structure and function of the female reproductive organs in Wnt10a knockout (KO) mice. The expression of β-catenin signaling was significantly lower in the ovaries of the Wnt10a KO mice compared with wild-type (WT) mice. In addition, the estrous cycles were disrupted, ovarian follicles were diminished, and endometria were thinner, accompanied by lower serum estrogen levels, and higher testosterone and progesterone levels in Wnt10a KO mice. The expression of the ovarian cytochrome P450 family 19 subfamily A member 1 (Cyp19a1) was significantly lower in Wnt10a KO mice. We detected no significant changes in the levels of the gonadotropins between WT and KO mice. Together, our findings indicate that deficiency of Wnt10a causes female infertility through β-catenin and Cyp19a1signaling pathways in mice.

We aimed to investigate the effects of maternal chewing on prenatal stress-induced cognitive impairments in the offspring and to explore the molecular pathways of maternal chewing in a mice model. Maternal chewing ameliorated spatial learning impairments in the offspring in a Morris water maze test. Immunohistochemistry and Western blot findings revealed that maternal chewing alleviated hippocampal neurogenesis impairment and increased the expression of hippocampal brain-derived neurotrophic factor in the offspring. In addition, maternal chewing increased the expression of glucocorticoid receptor (GR) and 11&beta, hydroxysteroid dehydrogenase isozyme 2 (11&beta, HSD2) and decreased the expression of 11&beta, HSD1 in the placenta, thereby attenuating the increase of glucocorticoid in the offspring. Furthermore, maternal chewing increased the expression of 11&beta, HSD2, FK506-binding protein 51 (FKBP51) and FKBP52 and decreased the expression of 11&beta, HSD1, thereby increasing hippocampal nuclear GR level. In addition, maternal chewing attenuated the increase in expression of DNMT1 and DNMT3a and the decrease in expression of histone H3 methylation at lysine 4, 9, 27 and histone H3 acetylation at lysine 9 induced by prenatal stress in the offspring. Our findings suggest that maternal chewing could ameliorate prenatal stress-induced cognitive impairments in the offspring at least in part by protecting placenta barrier function, alleviating hippocampal nuclear GR transport impairment and increasing the hippocampal brain-derived neurotrophic factor (BDNF) level.

Knee osteoarthritis (OA) is one of the most common musculoskeletal diseases and osteophytes area frequent radiographic feature of knee OA. The osteophyte structure in knee OA, however, is not well elucidated. This study aimed to clarify the three-dimensional microstructural characteristics of osteophytes in the medial compartment of the knee in knee OA patients using micro-computed tomography (micro-CT). We hypothesized that the morphology of osteophytes would differ from that of the neighboring normal cancellous bones. Ten medial compartment knee OA patients with Kellgren-Lawrence grade 4 severity were enrolled in the study, and all patients underwent total knee arthroplasty. Osteophytes and cancellous bones were obtained from the medial femoral condyle. The three-dimensional trabecular bone microstructure was analyzed by quantitative micro-CT using image analysis software. The trabecular bone volume fraction and trabecular number were significantly lower in osteophytes than in cancellous bones. Consistently, trabecular separation was significantly higher in osteophytes. Osteophytes exhibited disorganized trabecular orientation, trabecular perforation, disruption, and complete disconnection. These findings suggest that osteophytes are functionally fragile.

Although the understanding of the complex pathogenesis for osteoporosis is appreciable, the underlying mechanism is not yet fully elucidated. There is a great need to further characterize the available animal models in osteoporosis research. The senescence-accelerated mouse prone 6 (SAMP6) mice have been developed as the spontaneous experimental model for senile osteoporosis. Here, we provide a comprehensive overview of current research regarding the bone morphological and molecular alterations and the possible mechanisms involved in these changes. There were significant decrease in trabecular bone mass at the axial and appendicular skeletal sites, with no marked alterations of cortical bone. Decreased bone formation on the endosteal surface and trabecular bone, and increased bone marrow adiposity were observed in SAMP6 mice. The elevated expression level of proliferator activator gamma (PPARγ) in the bone marrow suggest that PPARγ might regulate osteoblastic bone formation negatively in SAMP6 mice. The expression level of secreted frizzled-related protein 4 (Sfrp4) was found to be higher in SAMP6 mice. Sfrp4 is considered to suppress osteoblastic proliferation mediated by inhibition of Wnt signaling pathway. These findings may help us to gain more insight into the potential mechanism of senile osteoporosis.

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.

Objective To examine whether maternal chewing affects prenatal stress-induced behavioral alternations associated with the changes in apoptosis-related proteins and serotonin pathway of the mouse offspring. Design Pregnant mice were assigned to control, stress, and stress/chewing groups. Stress mice were placed in restraint tubes, from gestational day 12 until parturition. Stress/chewing mice were given a wooden stick for chewing during stress period. Morris water maze and hole-board tests were applied for behavioral alterations in one-month-old male pups. Hippocampal mRNA expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) was analyzed by quantitative real-time PCR. Serotonin and tryptophan hydroxylase expression level in the dorsal raphe nucleus was investigated immunohistochemically. Results Prenatal stress impaired the spatial learning, induced anxiety-like behavior, increased the ratio of hippocampal Bax/Bcl-2 expression, and decreased the expression of serotonin and tryptophan hydroxylase in dorsal raphe nucleus of the offspring. Maternal chewing ameliorated prenatal stress-induced cognitive impairment, anxiety-like behavior, and attenuated the increased ratio of hippocampal Bax/Bcl-2 expression, and the downregulated serotonin signaling in dorsal raphe nucleus of the offspring. Conclusions Our results indicate that maternal chewing could improve prenatal stress-related anxiety-like behavior and cognitive impairment in mouse offspring, at least in part by affecting hippocampal apoptotic response and central serotonin pathway.

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

Objective Tooth loss induced neurological alterations through activation of a stress hormone, corticosterone. Age-related hippocampal morphological and functional changes were accelerated by early tooth loss in senescence-accelerated mouse prone 8 (SAMP8). In order to explore the mechanism underlying the impaired hippocampal function resulting from early masticatory dysfunction due to tooth loss, we investigated the effects of early tooth loss on plasma corticosterone levels, learning ability, neurogenesis, and synaptophysin expression in the hippocampus later in life of SAMP8 mice. Design We examined the effects of tooth loss soon after tooth eruption (1 month of age) on plasma corticosterone levels, learning ability in the Morris water maze, newborn cell proliferation, survival and differentiation in the hippocampal dentate gyrus, and synaptophysin expression in the hippocampus of aged (8 months of age) SAMP8 mice. Results Aged mice with early tooth loss exhibited increased plasma corticosterone levels, hippocampus-dependent learning deficits in the Morris water maze, decreased cell proliferation, and cell survival in the dentate gyrus, and suppressed synaptophysin expression in the hippocampus. Newborn cell differentiation in the hippocampal dentate gyrus, however, was not affected by early tooth loss. Conclusion These findings suggest that learning deficits in aged SAMP8 mice with tooth loss soon after tooth eruption are associated with suppressed neurogenesis and decreased synaptophysin expression resulting from increased plasma corticosterone levels, and that long-term tooth loss leads to impaired cognitive function in older age.

We examined whether chewing behavior affects the tumor progression-enhancing impact of psychological stress. Human breast cancer cell line (MDA-MB-231) cells were inoculated into the mammary fat pads of athymic nude mice. The mice were assigned randomly to control, stress, and stress+chewing groups. Psychological stress was created by keeping mice in a transparent restraint cylinder for 45 min, three times a day, for 35 days after cell inoculation. Animals in the stress+chewing group were provided with a wooden stick for chewing on during the psychological stress period. Chewing behavior remarkably inhibited the tumor growth accelerated by the psychological stress. Immunohistochemical and Western blot findings revealed that chewing behavior during psychological stress markedly suppressed tumor angiogenesis and cell proliferation. In addition, chewing behavior decreased serum glucocorticoid levels and expressions of glucocorticoid and β2-adrenergic receptors in tumors. Chewing behavior decreased expressions of inducible nitric oxide synthase and 4-hydroxynonenal, and increased expression of superoxide dismutase 2 in tumors. Our findings suggest that chewing behavior could ameliorate the enhancing effects of psychological stress on the progression of breast cancer, at least partially, through modulating stress hormones and their receptors, and the subsequent signaling pathways involving reactive oxygen and nitrogen species.

Objective Prolonged mild stress due to tooth loss leads to morphologic and functional alterations of the hippocampus, as well as cognitive memory impairments in aged animals. An enriched environment improves stress-induced hippocampus-dependent cognitive impairments. The potential mechanisms underlying the beneficial effects of an enriched environment, however, remain unclear. In the present study, we investigated whether an enriched environment affects morphologic remodeling of the hippocampal myelin, synapses, and spatial learning deficits caused by tooth loss in aged senescence-accelerated mouse strain P8 (SAMP8) mice. Design SAMP8 mice (8 months old) with either teeth intact or teeth extracted were raised in a standard or enriched environment for three weeks. Spatial learning and memory ability was evaluated in a Morris water maze test. The morphologic features of the myelin sheath and synapses in the hippocampus were investigated by electron microscopy. Results Mice with tooth loss had a thinner myelin sheaths and shorter postsynaptic densities in the hippocampal CA1 region, and impaired hippocampus-dependent spatial learning ability. Exposure to an enriched environment ameliorated the hypomyelination and synaptic alterations, and spatial learning and memory impairments induced by tooth loss in aged SAMP8 mice. Conclusion Our findings indicate that an enriched environment ameliorates hippocampal hypomyelination and synapse morphologic abnormalities, as well as learning deficits induced by tooth loss in aged SAMP8 mice.

Background and objective In humans, occlusal disharmony may cause various physical complaints, including head and neck ache, stiffness in the shoulder and neck, and arthrosis of the temporomandibular joints. Occlusal disharmony induced by raising the bite in rodents, increases plasma corticosterone levels, which leads to morphologic changes in the hippocampus and altered hippocampus-related behavior. The paraventricular nucleus (PVN) of the hypothalamus regulates the hypothalamic-pituitary-adrenal system. Chronically stressed animals exposed to a novel stress exhibit higher adrenocorticotropic hormone levels than naive control animals. We hypothesized that there would be different response of the corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) to a novel acute stress with occlusal disharmony. Design In order to investigate how exposure of mice with occlusal disharmony to a novel acute stress (restraint stress) affects the PVN, we induced occlusal disharmony by raising the vertical dimension of the bite (bite-raised condition) and examined the expression of corticotrophin releasing hormone (CRH) mRNA and arginine vasopressin (AVP) mRNA in mouse PVN. Results CRH mRNA expression was increased in the PVN of the bite-raised group 90 min after the bite-raising procedure, but the expression was recovered to the control level at 14 days. AVP mRNA expression in the PVN was normal at 90 min, and increased significantly 14 days after the bite-raising procedure. Exposure to restraint stress in the bite-raised mice induced a significant increase in CRH mRNA expression in the PVN. Conclusions The bite-raising procedure induced a rapid CRH mRNA response and a slower AVP mRNA response in the parvocellular PVN of the hypothalamus. Exposure to a novel stress following the bite-raising procedure further reinforced the CRH stress response. Thus, occlusal disharmony, such as that induced by raising the bite, may be a risk factor for hypersensitivity to a novel stress.

Yokukansan (YKS) is a traditional Japanese herbal medicine. It has been currently applied for treating behavioral and psychological symptoms of dementia in Japan. We investigated the effect of YKS on learning ability, hippocampal cell proliferation, and neural ultrastructural features in senescence-accelerated mouse prone 8 (SAMP8), a proposed animal model of Alzheimer's disease. Five-month-old male SAMP8 mice were randomly assigned to control and experimental groups. The control group had drug-free water ad libitum. The experimental mice were given 0.15% aqueous solution of YKS orally for eight weeks. Learning ability was assessed in Morris water maze test. Hippocampal cell proliferation was investigated using bromodeoxyuridine immunohistochemical method. The neural ultrastructural features, including myelin sheath and synapse, were investigated electron microscopy. Administration with YKS improved the hippocampal cell proliferation in dentate gyrus, and ameliorated learning impairment in SAMP8 mice. Numerous lipofuscin inclusions were presented in hippocampal neurons of the control mice. However, little were found after treatment with YKS. Myelin sheath was thicker and postsynaptic density length was longer after treatment with YKS. Administration with YKS ameliorated learning impairment in SAMP8 mice, mediated at least partially via delaying neuronal aging process, neurogenesis, myelin sheath and synaptic plasticity in the hippocampus. These results suggest that YKS might be effective for preventing hippocampus-dependent cognitive deficits with age.

Wnt10a is a member of the WNT family. Although deficiency of this gene causes symptoms related to teeth, hair, nails, and skin, we recently demonstrated a new phenotype of Wnt10a knockout (KO) mice involving bone and fat. The in vivo effect of the Wnt10a gene on bone and fat is unclear, and the relationship between bone/fat and muscle in Wnt10a signaling is also interesting. We aimed to evaluate the tissue changes in Wnt10a KO mice compared to wild-type mice and show the findings as a starting point to unravel the underlying mechanisms of in vivo interactions involving Wnt10a in bone, fat and muscle. Trabecular bone loss in the lower limbs of Wnt10a mice and decreased bone mineralization were observed. The adipose tissue in bone marrow was also decreased, and adipocyte differentiation was reduced. The body fat mass in Wnt10a KO mice was decreased, and white adipocytes in subcutaneous fat were converted to beige adipocytes. The muscle weight of the lower limbs was not decreased despite trabecular bone loss, but Gdf8/myostatin expression was reduced in the subcutaneous fat and gastrocnemius muscles of Wnt10a KO mice. Thus, in vivo deletion of Wnt10a inhibited osteogenic activity, promoted beige adipogenesis of white adipocytes and maintained muscle mass. These results suggest that regulation of Gdf8 by Wnt10a may help maintain the muscle mass of Wnt10a KO mice. This study was the first to histologically evaluate the bone, fat and muscle phenotypes of Wnt10a KO mice. The results of this study, which were obtained by investigating the three tissues together, could influence the understanding of in vivo interactions involving the Wnt10a gene.

Objective To investigate whether maternal chewing during prenatal stress alters the responsivity of young offspring to novel stress, we examined the expression of hippocampal glucocorticoid receptors and mineralocorticoid receptors, and the levels of hypothalamic corticotropin-releasing hormone in young adult mouse offspring of dams exposed to restraint stress during pregnancy. Design To induce stress, the dams were placed in a ventilated restraint tube for 45 min each day from day 12 of pregnancy through parturition. While restrained in the tube, one group of dams was provided a wooden stick for chewing. Hippocampal expression of glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid was assessed in 1-month-old pups. Hypothalamic expression of corticotropin-releasing hormone messenger ribonucleic acid was examined before and after exposing the offspring to a novel stressor. Results Prenatal stress significantly decreased hippocampal expression of both glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid in the offspring, and increased the expression of corticotropin-releasing hormone messenger ribonucleic acid in the hypothalamic paraventricular nucleus in the offspring after novel stress exposure. Maternal chewing during exposure to prenatal stress attenuated the decreased hippocampal expression of both glucocorticoid receptor and mineralocorticoid receptor messenger ribonucleic acid, and the increased corticotropin-releasing hormone messenger ribonucleic acid expression in the hypothalamic paraventricular nucleus in the offspring. Conclusions Downregulation of hippocampal glucocorticoid receptor and mineralocorticoid receptor expression in offspring due to prenatal stress, which may be associated with increased susceptibility to novel stress in adulthood, are attenuated by allowing the dams to chew on a wooden stick.

Prenatal stress (PS) induces learning deficits and anxiety-like behavior in mouse pups by increasing corticosterone levels in the dam. We examined the effects of maternal chewing during PS on arginine vasopressin (AVP) mRNA expression in the dams and on neurogenesis, brain-derived neurotrophic factor (BDNF) mRNA expression, learning deficits and anxiety-like behavior in the offspring. Mice were divided into control, stress and stress/chewing groups. Pregnant mice were exposed to restraint stress beginning on day 12 of pregnancy and continuing until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint stress. PS significantly increased AVP mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus in the dams. PS also impaired learning ability, suppressed neurogenesis and BDNF mRNA expression in the hippocampus, and induced anxiety-like behavior in the offspring. Chewing during PS prevented the PS-induced increase in AVP mRNA expression of the PVN in the dams. Chewing during PS significantly attenuated the PS-induced learning deficits, anxiety-like behavior, and suppression of neurogenesis and BDNF mRNA expression in the hippocampus of the offspring. Chewing during PS prevented the increase in plasma corticosterone in the dam by inhibiting the hypothalamic-pituitary-adrenal axis activity, and attenuated the attenuated the PS-induced suppression of neurogenesis and BDNF expression in the hippocampus of the pups, thereby ameliorating the PS-induced learning deficits and anxiety-like behavior. Chewing during PS is an effective stress-coping method for the dam to prevent PS-induced deficits in learning ability and anxiety-like behavior in the offspring.

Osteoporosis, the most common metabolic skeletal disease, is characterized by decreased bone mass and deteriorated bone quality, leading to increased fracture risk. With the aging of the population, osteoporotic fracture is an important public health issue. Organisms are constantly exposed to various stressful stimuli that affect physiological processes. Recent studies showed that chronic psychological stress is a risk factor for osteoporosis by various signaling pathways. The purpose of this article is to review the recent progress of the association between chronic psychological stress and osteoporosis. Increasing evidence confirms the physiological importance of the central nervous system, especially the hypothalamus, in the regulation of bone metabolism. Both animal and human studies indicate that chronic psychological stress induces a decrease of bone mass and deterioration of bone quality by influencing the hypothalamic-pituitary-adrenocortical (HPA) axis, sympathetic nervous system, and other endocrine, immune factors. Active mastication, proven to be an effective stress-coping behavior, can attenuate stress-induced neuroendocrine responses and ameliorate stress-induced bone loss. Therefore, active mastication may represent a useful approach in preventing and/or treating chronic stress-associated osteoporosis. We also discuss several potential mechanisms involved in the interaction between chronic stress, mastication and osteoporosis. Chronic stress activates the HPA axis and sympathetic nervous system, suppresses the secretion of gonadal hormone and growth hormone, and increases inflammatory cytokines, eventually leading to bone loss by inhibiting bone formation and stimulating bone resorption.

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity.

Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring.

The above article originally published with an error present in Table 2 and is now presented correctly in this article.

Background and objective Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss. Design Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. Results Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability. Conclusion These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss.