Abstract

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.

Highlights

  • All living organisms must maintain a complex dynamic homeostasis that is constantly challenged by various external and internal disturbances or stressors

  • Acute and chronic stress exposure impairs hippocampal neurogenesis, reduces progenitor cell proliferation, and suppresses neuronal differentiation and cell survival in the hippocampal dentate gyrus [15,16,45,47,58]. In addition to these direct effects of acute and chronic stress on hippocampal progenitor cells in affected animals, prenatal stress and exposure to excess GCs in utero alter the brain development and maturation of littermates, which can result in adverse consequences in later adult life, reducing the lifespan of neurogenesis in the hippocampal dentate gyrus, and leading to hippocampus-dependent cognitive deficits [21,22,23]. These findings indicate that stress affects adult hippocampal neurogenesis, and has a transgenerational effect through transmitted epigenetic mechanisms, leading to lifelong effects in littermates when the pregnant mother is exposed to stressful conditions [60]

  • Masticatory stimulation could attenuate the hyperactivity of the HPA axis, improve the ability to cope with stress, and alleviate chronic stress-induced hippocampus-dependent cognitive deficits

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Summary

Introduction

All living organisms must maintain a complex dynamic homeostasis that is constantly challenged by various external and internal disturbances or stressors. Numerous human and animal studies indicate that masticatory dysfunction, acting as source of chronic stress, activates the HPA axis, leading to increases in circulating GC levels and precipitating various illnesses, such as hippocampus-dependent cognitive deficits, hypertension, cardiovascular disorders, and osteoporosis [18,19,20,21]. Recent studies indicate that masticatory stimulation or chewing during stressful conditions can ameliorate chronic stress-induced physical and psychological disorders by suppressing HPA axis hyperactivity [15,16,17,22,23]. Masticatory dysfunction activates the HPA axis, affecting physical, psychological, and social health, contributing to senile dementia, Alzheimer’s disease, and a declining quality of life in the elderly. The continuous increase in circulating GC levels induced by masticatory dysfunction disrupts the negative feedback system of the HPA axis, further enhancing the secretion of GCs

Occlusal Disharmony and the HPA Axis
Tooth Extraction and the HPA Axis
Masticatory Dysfunction and Hippocampal Function
Molecular Links between Masticatory Dysfunction and HPA Axis Hyperactivity
Masticatory Stimulation Preserves Hippocampal Function
Masticatory Stimulation Attenuates HPA Axis Activation
Conclusions
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