Shuu Fujiwara

Occlusal disharmony leads to learning deficits associated with decreased cellular proliferation in the hippocampal dentate gyrus of SAMP8 mice.

Occlusal disharmony is associated with increased plasma corticosterone levels, learning deficits, and morphologic alterations in the hippocampus via chronic stress. Here, we investigated the occlusal disharmony-induced impairment of hippocampal function. We first examined the effects of raising the bite on newborn cell proliferation in the hippocampal dentate gyrus (DG) in senescence-accelerated prone mice. Raising the bite significantly decreased cell proliferation in the hippocampal DG in an age-dependent manner. Immediately after raising the bite, cell proliferation decreased abruptly in the aged mice, then gradually increased, but did not recover to control levels within 2wk. Further, learning-induced cell proliferation was impaired in aged bite-raised mice. These findings suggest that occlusal disharmony induced by raising the bite impaired cell proliferation in the hippocampal DG, leading to learning deficits.

Effect of bite-raised condition on the hippocampal cholinergic system of aged SAMP8 mice

Occlusal disharmony induces chronic stress, which results in learning deficits in association with the morphologic changes in the hippocampus, e.g., neuronal degeneration and increased hypertrophied glial fibrillary acidic protein-positive cells. To investigate the mechanisms underlying impaired hippocampal function resulting from occlusal disharmony, we examined the effects of the bite-raised condition on the septohippocampal cholinergic system by assessing acetylcholine release in the hippocampus and choline acetyltransferase immunoreactivity in the medial septal nucleus in aged SAMP8 mice that underwent the bite raising procedure. Aged bite-raised mice showed decreased acetylcholine release in the hippocampus and a reduced number of choline acetyltransferase-immunopositive neurons in the medial septal nucleus compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice enhances the age-related decline in the septohippocampal cholinergic system, leading to impaired learning.

Effects of occlusal disharmony on the hippocampal dentate gyrus in aged senescence-accelerated mouse prone 8 (SAMP8).

BACKGROUND AND OBJECTIVE Malocclusion induced by raising the bite causes chronic stress. Chronic stress leads to increased plasma corticosterone levels and impaired hippocampal function due to impaired neurogenesis or increased apoptosis in the hippocampus. The present study aimed to clarify the mechanisms underlying the impaired hippocampal function induced by the bite-raised condition in aged senescence-accelerated mouse prone 8 (SAMP8). DESIGN Nine-month-old aged SAMP8 mice were randomly divided into control and bite-raised groups. The vertical dimension of the bite was raised by applying resin to the molars. We evaluated newborn cell proliferation, survival, differentiation, and apoptosis in the hippocampal dentate gyrus (DG). Hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. RESULTS The bite-raised mice exhibited a significant decrease in proliferation, survival, and differentiation of newborn cells into neurons in the hippocampal DG compared with controls. The number of apoptotic cells in the hippocampal DG was increased at 7 and 14 days after the bite-raising procedure. Expression of BDNF protein and mRNA in the hippocampus was also decreased in the bite-raised mice. CONCLUSION Bite-raised aged SAMP8 mice exhibited decreased neurogenesis, increased apoptosis in the hippocampal DG, and decreased hippocampal BDNF expression, in association with hippocampus-dependent learning and memory deficits.

Novel stress increases hypothalamic-pituitary-adrenal activity in mice with a raised bite

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 90min after the bite-raising procedure, but the expression was recovered to the control level at 14days. AVP mRNA expression in the PVN was normal at 90min, and increased significantly 14days 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.

Usefulness of an energy-binned photon-counting x-ray detector for dental panoramic radiographs

A newly developed dental panoramic radiography system is equipped with a photon-counting semiconductor detector. This photon-counting detector acquires transparent X-ray beams by dividing them into several energy bands. We developed a method to identify dental materials in the patient’s teeth by means of the X-ray energy analysis of panoramic radiographs. We tested various dental materials including gold alloy, dental amalgam, dental cement, and titanium. The results of this study suggest that X-ray energy scattergram analysis could be used to identify a range of dental materials in a patient’s panoramic radiograph.

Effects of occlusal disharmony on the cholinergic system in the septohippocampal tract of SAMP8 mice

Schizophrenia is a severe psychiatric disorder with a worldwide prevalence of about 1%. Multiple independent studies based on cytokine measurements indicate a shift from Th1-like to Th2-like immune reactivity. However, the molecular bases of the shift in immune cells observed in schizophrenic patients remain unclear. In order to determine molecular bases of the shift in helper T cells, and the involvement into the pathogenesis of schizophrenia, we developed a research system to evaluate comprehensive gene expression profiles of Th1 and Th2 cells using fluorescence-activated cell sorting and microarray technologies. After obtaining written informed consent following the IRB-approved protocol, peripheral blood lymphocytes from 18 patients with schizophrenia and 18 control subjects were collected by Ficoll differential centrifugation. Lymphocytes were stained with anti-CD4-FITC, CXCR3-APC, CCR45-PE. Th1 (CD4+/CXCR3+) and Th2 (CD4+/CCR4+) cell sorting experiments were performed using FACS Aria. Extracted total RNA sample from each cell was amplified and applied on Illumina Human-6v2 BeadChips to analyze global changes in genome-wide mRNA expression levels. FACSarray gene expression profiling determined 223 increased and 586 decreased genes in Th1 helper T cells, and 87 increased and 108 decreased genes in Th2 helper T cells from schizophrenic patients, compared to control subjects. Genes dysregulated in Th1 genes of schizophrenic patients contain zinc finger genes and biopolymer modification related genes. Genes dysregulated in Th2 genes of schizophrenic patients include telomere maintenance related genes and chromosomal protein coding genes. These genes may be relevant to the Th1/Th2 imbalance observed in schizophrenic patients, and the pathophysiology of the disease.