Long-term sorbitol consumption affects the hippocampus and alters cognitive function in aged mice.

The systemic effects of the artificial sweetener sorbitol on older adult individuals have not been elucidated. We assessed the effects of sorbitol consumption on cognitive and gingival health in a mouse model. Aged mice were fed 5% sorbitol for 3 months before their behavior was assessed, and brain and gingival tissues were collected. Long-term sorbitol consumption inhibited gingival tissue aging in aged mice. However, it caused cognitive decline and decreased brain-derived neurotrophic factor (BDNF) in the hippocampus. Sorbitol consumption did not affect homeostatic function; however, it may exert effects within the brain, particularly in the hippocampus.

Premature gray hair development in the interbrow region owing to the loss of maxillary first molars in young mice.

The exact sites of premature hair graying and whether tooth loss causes this condition remain unknown. In this study, we aimed to explore the effect of reduced mastication on premature hair graying. Maxillary first molars were extracted from young mice, and the mice were observed for 3 months, along with non-extraction control group mice. After 3 months, gray hair emerged in the interbrow region of mice in the tooth extraction group but not in the control group. The expression of tyrosinase-related protein-2 (TRP-2) mRNA was lower in the interbrow tissues of young mice without maxillary molars than in those with maxillary molars. Tooth loss leads to interbrow gray hair growth, possibly because of weakened trigeminal nerve input, suggesting that reduced mastication causes premature graying. Thus, prompt prosthetic treatment after molar loss is highly recommended.

Associations between dietary diversity and high sensitive C-reactive protein among Japanese workers: findings of a cross-sectional and longitudinal study.

PURPOSE: To clarify the association between dietary diversity and inflammatory status in Japanese workers. METHODS: Of 1,460 men and women aged 20-64 years in 2010 (baseline), those who were followed-up at least once between 2011 and 2018 were included in this study; 1,433 participants and 745 participants were included in the cross-sectional and longitudinal analyses, respectively. Dietary intake was assessed using a food frequency questionnaire at baseline, and the dietary diversity score was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). High-sensitivity C-reactive protein (hs-CRP) was taken to indicate inflammatory status at the baseline and follow-up surveys. In the cross-sectional analysis using baseline data, a generalized linear model was used to calculate adjusted means and 95% confidence intervals (CIs) for hs-CRP according to the QUANTIDD score. In the longitudinal analysis, generalized estimating equations were used to calculate the adjusted mean (95% CI) for hs-CRP in follow-up according to the QUANTIDD score at baseline. RESULTS: In the cross-sectional analysis, the hs-CRP concentration in male participants was significantly lower in those who had a high QUANTIDD score (adjusted mean [95% CI]: 0.074 [0.009-0.140] mg/dL in the lower group vs. 0.038 [-0.029-0.105] mg/dL in the higher group, p-value = 0.034). In the longitudinal analysis, the hs-CRP concentration of male participants also tended to be lower in those with higher QUANTIDD scores (p-value = 0.103). In both the cross-sectional and longitudinal analyses in women, there was no significant difference between the lower and higher QUANTIDD score groups. CONCLUSION: These findings suggest that, in male Japanese workers, higher dietary diversity might be important for maintaining a low inflammatory status.

Associations between dietary diversity and dyslipidemia among Japanese workers: cross-sectional study and longitudinal study findings.

OBJECTIVE: The aim of this study was to determine the associations between dietary diversity and risk of dyslipidemia in Japanese workers. METHODS: The cross-sectional study included 1399 participants aged 20-63 years and the longitudinal study included 751 participants aged 20-60 years in 2012-2013 (baseline) who participated at least once from 2013 to 2017 with cumulative participation times of 4.9 times. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity score (DDS) was determined using the Quantitative Index for Dietary Diversity. Dyslipidemia was diagnosed when at least one of the following conditions was met: hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, high non-HDL-cholesterol, and a history of dyslipidemia. Multivariable logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for dyslipidemia with control of confounding factors in cross-sectional analysis. Generalized estimating equations were used for calculating the ORs (95% CI) for dyslipidemia in the follow-up period according to the DDS at baseline with control of confounding factors in longitudinal analysis. RESULTS: Cross-sectional analysis showed that the highest DDS reduced the odds of dyslipidemia in men (OR [95% CI] in Tertile 3: 0.67 [0.48-0.95], p value = 0.023). In longitudinal analysis, a moderate DDS reduced the risk of dyslipidemia (OR [95% CI] in Tertile 2: 0.21 [0.07-0.60], p value = 0.003) in women. CONCLUSIONS: The results of cross-sectional analysis in this study suggest that the higher diversity of diet might reduce the presence of dyslipidemia in men and the results of longitudinal analysis suggest that a moderate DDS might reduce the risk of dyslipidemia in women. Further studies are needed since the results of cross-sectional and longitudinal analyses in this study were inconsistent.

Imaging of muscle activity-induced morphometric changes in fibril network of myofascia by two-photon microscopy.

Myofascia, deep fascia enveloping skeletal muscles, consists of abundant collagen and elastin fibres that play a key role in the transmission of muscular forces. However, understanding of biomechanical dynamics in myofascia remains very limited due to less quantitative and relevant approaches for in vivo examination. The purpose of this study was to evaluate the myofascial fibril structure by means of a quantitative approach using two-photon microscopy (TPM) imaging in combination with intravital staining of Evans blue dye (EBD), a far-red fluorescence dye, which potentially labels elastin. With focus on myofascia of the tibial anterior (TA) muscle, the fibril structure intravitally stained with EBD was observed at the depth level of collagen fibrous membrane above the muscle belly. The EBD-labelled fibril structure and orientation in myofascia indicated biomechanical responses to muscle activity and ageing. The orientation histograms of EBD-labelled fibrils were significantly modified depending upon the intensity of muscle activity and ageing. Moreover, the density of EBD-labelled fibrils in myofascia decreased with habitual exercise but increased with muscle immobilization or ageing. In particular, the diameter of EBD-labelled fibrils in aged mice was significantly higher. The orientation histograms of EBD-labelled fibrils after habitual exercise, muscle immobilization and ageing showed significant differences compared to control. Indeed, the histograms in bilateral TA myofascia of exercise mice made simple waveforms without multiple sharp peaks, whilst muscular immobilization or ageing significantly shifted a histogram with sustaining multiple sharp peaks. Therefore, the dynamics of fibre network with EBD fluorescence in response to the biomechanical environment possibly indicate functional tissue adaptation in myofascia. Furthermore, on the basis of the knowledge that neutrophil recruitment occurs locally in working muscles, we suggested the unique reconstruction mechanism involving neutrophilic elastase in the myofascial fibril structure. In addition to the elastolytic susceptibility of EBD-labelled fibrils, distinct immunoreactivities and activities of neutrophil elastase in the myofascia were observed after electric pulse stimulation-induced muscle contraction for 15 min. Our findings of EBD-labelled fibril dynamics in myofascia through quantitative approach using TPM imaging and intravital fluorescence labelling potentially brings new insights to examine muscle physiology and pathology.

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren's Syndrome Model Mice.

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4+ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren's syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.

Associations of dietary diversity with allergic diseases in Japanese workers: a cross-sectional study.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the associations of dietary diversity with prevalences of allergic diseases. METHODS AND STUDY DESIGN: The participants were 1,317 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics and current medical histories of allergic diseases using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The ORs and 95% CIs for each of the allergic diseases with a 1 standard deviation (SD) increase in the QUANTIDD score were estimated, controlling for age, family history of allergic diseases, education, smoking, drinking, physical activity, energy intake and BMI. RESULTS: Higher dietary diversity showed significant inverse dose-response relationships with allergic diseases and allergic rhinitis in women. Multivariate-adjusted ORs (95% CI) for allergic diseases and allergic rhinitis with 1 SD increase in the QUANTIDD score were 0.77 (95% CI: 0.60-0.98, p=0.037) and 0.69 (95% CI: 0.53-0.90, p=0.007), respectively, in women. There were no significant associations between dietary diversity and allergic diseases in men. CONCLUSIONS: The results indicate that there is an inverse association between higher dietary diversity and allergic rhinitis in Japanese female workers.

Potential Role of Free Fatty Acids in the Pathogenesis of Periodontitis and Primary Sjögren's Syndrome.

Clinical studies have shown that metabolic disorders such as type 2 diabetes and dyslipidemia are associated with increased risk of oral-related diseases, such as periodontitis and Sjögren's syndrome. Although changes in the immune system are critical in both of these metabolic disorders and oral-related diseases, the mechanism underlying the interaction between these diseases remains largely unknown. Obesity and type 2 diabetes are known to be associated with higher concentrations of free fatty acids in blood. Among free fatty acids, saturated fatty acids such as palmitic acid have been demonstrated to induce inflammatory responses mainly via the innate immune systems, and to be involved in the pathogenesis of type 2 diabetes in tissues such as adipose tissue, liver, pancreas, and skeletal muscle. Here, we highlight recent advances in evidence for the potential involvement of palmitic acid in the pathogenesis of periodontitis and Sjögren's syndrome, and discuss the possibility that improvement of the lipid profile could be a new strategy for the treatment of these diseases.

Possible Involvement of Palmitate in Pathogenesis of Periodontitis.

Type 2 diabetes (T2D) is characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been suggested to promote inflammatory responses. Although many epidemiological studies have shown a link between periodontitis and T2D, little is known about the clinical significance of SFAs in periodontitis. In this study, we showed that gingival fibroblasts have cell-surface expression of CD36, which is also known as FAT/fatty acid translocase. Moreover, CD36 expression was increased in gingival fibroblasts of high-fat diet-induced T2D model mice, compared with gingival fibroblasts of mice fed a normal diet. DNA microarray analysis revealed that palmitate increased mRNA expression of pro-inflammatory cytokines and chemokines in human gingival fibroblasts (HGF). Consistent with these results, we confirmed that palmitate-induced interleukin (IL)-6, IL-8, and CXCL1 secretion in HGF, using a cytokine array and ELISA. SFAs, but not an unsaturated fatty acid, oleate, induced IL-8 production. Docosahexaenoic acid (DHA), which is one of the omega-3 polyunsaturated fatty acids, significantly suppressed palmitate-induced IL-6 and IL-8 production. Treatment of HGF with a CD36 inhibitor also inhibited palmitate-induced pro-inflammatory responses. Finally, we demonstrated that Porphyromonas gingivalis (P.g.) lipopolysaccharide and heat-killed P.g. augmented palmitate-induced chemokine secretion in HGF. These results suggest a potential link between SFAs in plasma and the pathogenesis of periodontitis.

Palmitate-stimulated monocytes induce adhesion molecule expression in endothelial cells via IL-1 signaling pathway.

Increased intake of saturated fatty acids (SFAs), such as palmitate (Pal), is linked to a higher risk of type 2 diabetes and cardiovascular disease. Although recent studies have investigated the direct effects of SFAs on inflammatory responses in vascular endothelial cells, it remains unknown whether SFAs also induce these responses mediated by circulating cells. In this study, especially focused on adhesion molecules and monocytes, we investigated the indirect effects of Pal on expression and release of ICAM-1 and E-selectin in vascular endothelial cells. Phorbol 12-myristate 13-acetate (PMA)-treated THP-1 (pTHP-1) cells and human monocytes were stimulated with various free fatty acids (FFAs). SFAs, but not unsaturated fatty acids (UFAs), increased interleukin (IL)-1ß secretion and decreased IL-1 receptor antagonist (IL-1Ra) secretion, resulting in an increase in the IL-1ß/IL-1Ra secretion ratio. UFAs dose-dependently inhibited the increase in IL-1ß secretion and decrease in IL-1Ra secretion induced by Pal. Moreover, in human aortic and vein endothelial cells, expression and release of ICAM-1 and E-selectin were induced by treatment with conditioned medium collected from Pal-stimulated pTHP-1 cells and human monocytes, but not by Pal itself. The up-regulated expression and release of adhesion molecules by the conditioned medium were mostly abolished by recombinant human IL-1Ra supplementation. These results suggest that the Pal-induced increase in the ratio of IL-1ß/IL-1Ra secretion in monocytes up-regulates endothelial adhesion molecules, which could enhance leukocyte adhesion to endothelium. This study provides further evidence that IL-1ß neutralization through receptor antagonism may be useful for preventing the onset and development of cardiovascular disease.

Correction: Furukawa et al. Long-Term Soft-Food Rearing in Young Mice Alters Brain Function and Mood-Related Behavior. Nutrients 2023, 15, 2397.

In the original publication [...].

Effects of tooth loss on behavioral and psychological symptoms of dementia in app knock-in mice.

OBJECTIVES: Many patients with Alzheimer's disease (AD) experience behavioral and psychological symptoms of dementia (BPSD), which significantly affect their quality of life. It is known that 5-Hydroxytryptamine (5-HT) plays a crucial role in the development of BPSD. While the relationship between tooth loss and AD symptoms has been acknowledged, the aspect of aggression has not been focused on until now. Despite the established importance of 5-HT in BPSD, how tooth loss is related to the exacerbation of AD symptoms, especially in terms of aggression, remains largely unexplored. Although nutritional status is known to influence the progression of dementia, the specific effect of tooth loss on peripheral symptoms, notably aggression, is not well understood. METHODS: In our study, we conducted maxillary molar extractions in aged C57BL/6J and AppNL-G-F mice and observed their condition over a 3-month period. During this time, we documented significant behavioral and genetic differences between mice in the control groups and mice that underwent tooth extraction. Notably, mice that underwent tooth extraction exhibited a considerable decline in cognitive function and increased in aggression 3 months after tooth extraction compared with the control groups (C57BL/6J and AppNL-G-Fmice). RESULTS: Our findings suggest that molar loss may lead to reduced 5-HT levels in the hippocampus, possibly mediated by the trigeminal nerve, contributing to the development of aggression and BPSD in AD. CONCLUSION: This study sheds light on the intricate relationships between oral health, 5-HT, and AD symptoms, offering valuable insights into potential therapeutic avenues for managing BPSD in patients with dementia.

Long-Term Soft-Food Rearing in Young Mice Alters Brain Function and Mood-Related Behavior.

The relationship between caloric and nutrient intake and overall health has been extensively studied. However, little research has focused on the impact of the hardness of staple foods on health. In this study, we investigated the effects of a soft diet on brain function and behavior in mice from an early age. Mice fed a soft diet for six months exhibited increased body weight and total cholesterol levels, along with impaired cognitive and motor function, heightened nocturnal activity, and increased aggression. Interestingly, when these mice were switched back to a solid diet for three months, their weight gain ceased, total cholesterol levels stabilized, cognitive function improved, and aggression decreased, while their nocturnal activity remained high. These findings suggest that long-term consumption of a soft diet during early development can influence various behaviors associated with anxiety and mood regulation, including weight gain, cognitive decline, impaired motor coordination, increased nocturnal activity, and heightened aggression. Therefore, the hardness of food can impact brain function, mental well-being, and motor skills during the developmental stage. Early consumption of hard foods may be crucial for promoting and maintaining healthy brain function.

Long-Term Capsaicin Administration Ameliorates the Dysfunction and Astrogliosis of the Brain in Aged Mice with Missing Maxillary Molars.

Tooth loss and decreased masticatory function reportedly affect cognitive function; tooth loss allegedly induces astrogliosis and aging of astrocytes in the hippocampus and hypothalamus, which is a response specific to the central nervous system owing to homeostasis in different brain regions. Capsaicin, a component of red peppers, has positive effects on brain disorders in mice. Decreased expression of transient receptor potential vanilloid 1, a receptor of capsaicin, is associated with the development of dementia. In this study, we investigated the effect of capsaicin administration in aged mice (C57BL/6N mice) with reduced masticatory function owing to the extraction of maxillary molars to investigate preventive/therapeutic methods for cognitive decline attributed to age-related masticatory function loss. The results demonstrated that mice with impaired masticatory function showed decreased motor and cognitive function at the behavioral level. At the genetic level, neuroinflammation, microglial activity, and astrogliosis, such as increased glial fibrillary acidic protein levels, were observed in the mouse brain. The mice with extracted molars fed on a diet containing capsaicin for 3 months demonstrated improved behavioral levels and astrogliosis, which suggest that capsaicin is useful in maintaining brain function in cases of poor oral function and prosthetic difficulties.

Erythritol Can Inhibit the Expression of Senescence Molecules in Mouse Gingival Tissues and Human Gingival Fibroblasts.

Oral aging causes conditions including periodontal disease. We investigated how the sugar alcohol erythritol, which has anti-caries effects, impacts aging periodontal tissues and gingival fibroblasts in mice and humans in vivo and in vitro. Mice were classified into three groups: control groups of six-week-old (YC) and eighteen-month-old mice (AC) and a group receiving 5% w/w erythritol water for 6 months (AE). After rearing, RNA was extracted from the gingiva, and the levels of aging-related molecules were measured using PCR. Immunostaining was performed for the aging markers p21, γH2AX, and NF-κB p65. p16, p21, γH2AX, IL-1ß, and TNFα mRNA expression levels were higher in the gingiva of the AC group than in the YC group, while this enhanced expression was significantly suppressed in AE gingiva. NF-κB p65 expression was high in the AC group but was strongly suppressed in the AE group. We induced senescence in cultured human gingival fibroblasts using H2O2 and lipopolysaccharide before erythritol treatment, which reduced elevated senescence-related marker (p16, p21, SA-ß-gal, IL-1ß, and TNFα) expression levels. Knockdown of PFK or PGAM promoted p16 and p21 mRNA expression, but erythritol subsequently rescued pyruvate production. Overall, intraoral erythritol administration may prevent age-related oral mucosal diseases.

The Priming Potential of Interferon Lambda-1 for Antiviral Defense in the Oral Mucosa.

The oral mucosa is one of the first lines of the innate host defense system against microbial invasion. Interferon (IFN) lambda-1 (IFN-λ1), a type III IFN, exhibits type I IFN-like antiviral activity. In contrast to ubiquitously expressed type I IFN receptors, IFN-λ receptor 1 (IFN-λR1), which has higher affinity for type III IFNs than low-affinity interleukin (IL)-10 receptor 2, is mainly expressed on epithelial cells. Although IFN-λ1 has been shown to exert antiviral effects in the respiratory tract, gastrointestinal tract, and skin, the regulation of type III IFN receptor expression and its functions in the oral mucosa remain unclear. We herein showed the expression of IFN-λR1 in human gingival keratinocytes. The expression of IL-6, angiotensin-converting enzyme 2 (a critical molecule for severe acute respiratory syndrome coronavirus 2 infection), and IL-8 in human primary gingival keratinocytes (HGK) were significantly higher following treatments with either type I IFN (IFN-ß) or type II IFN (IFN-γ) than with IFN-λ1. However, the IFN-λ1 treatment strongly induced toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I), which mainly recognize viral nucleic acids, via the STAT1-mediated pathway. Furthermore, a stimulation with a RIG-I or TLR3 agonist promoted the production of IL-6, IL-8, and IFN-λ in HGK, which was significantly enhanced by a pretreatment with IFN-λ1. These results suggest that IFN-λ1 may contribute to the activation of innate immune responses to oral viral infections by up-regulating the expression of RIG-I and TLR3 and priming their functions in keratinocytes.

Molar loss induces hypothalamic and hippocampal astrogliosis in aged mice.

Age-related tooth loss impedes mastication. Epidemiological and physiological studies have reported that poor oral hygiene and occlusion are associated with cognitive decline. In the present study, we analyzed the mechanism by which decreased occlusal support following bilateral extraction of the maxillary first molars affects cognitive functions in young and aged mice and examined the expression of brain-function-related genes in the hippocampus and hypothalamus. We observed decreased working memory, enhanced restlessness, and increased nocturnal activity in aged mice with molar extraction compared with that in mice with intact molars. Furthermore, in the hypothalamus and hippocampus of molar-extracted aged mice, the transcript-level expression of Bdnf, Rbfox3, and Fos decreased, while that of Cdkn2a and Aif1 increased. Thus, decreased occlusal support after maxillary first molar extraction may affect cognitive function and activity in mice by influencing aging, neural activity, and neuroinflammation in the hippocampus and hypothalamus.

Analysis of senescence in gingival tissues and gingival fibroblast cultures.

OBJECTIVE: To determine senescence-associated changes in the gingival tissues of aged mice and gingival fibroblast cultures. MATERIALS AND METHODS: The production of senescence-associated ß-galactosidase (SA-ß-gal) and mRNA expression of p16, p21, interleukin (IL)-1ß, and tumor necrosis factor α (TNF-α) were evaluated in gingival tissues, gingival fibroblasts of 10- and 20-month-old C57BL/6NCrl mice, and multiple-passaged and hydrogen peroxide-stimulated human gingival fibroblasts (HGFs). Changes in molecular expression in HGF cultures due to senescent cell elimination by the senolytic drug ABT-263 (Navitoclax) were analyzed. RESULTS: Compared to 10-week-old mice, the 20-month-old mice had higher numbers of M1 macrophages. The proportion of cells expressing SA-ß-gal were also higher in 20- month-old mice than in 10-week-old-mice. Gingival fibroblasts in 20-month-old mice expressed less collagen 1a1, collagen 4a1, and collagen 4a2 mRNA than those in 10-week-old mice. Compared to control cells, H2O2 treated HGF cells expressed higher levels of SA-ß-gal and p16, p21, IL-1ß, and TNF-α. Furthermore, ABT-263 suppressed HGF cell expression of cytokines after senescence induction. CONCLUSIONS: Senescence-associated changes were observed in the gingival tissues of aged mice and HGF cultures. In addition, the potential of senolytic drugs to modify aging-related changes in the gingiva was shown.

Effect of green propolis extracts on experimental aged gingival irritation in vivo and in vitro.

OBJECTIVES: Tooth bleaching has become one of the most frequently requested esthetic procedures in dental practice. A side effect of bleaching is gingival irritation. This study examined the efficacy of propolis to treat gingival irritation caused by bleaching in vivo and in vitro. METHODS: Gingival irritation was mimicked by a mild burn injury to oral mucosa in young (10 week old) and aged (18 month old) mice. Propolis ointment was immediately applied to the burn area. After 24 h, gingiva was collected to determine the efficacy of propolis by hematoxylin and eosin staining and real-time polymerase chain reaction (PCR). RESULTS: Topical application of propolis ointment reduced the infiltration of inflammatory cells at irritated sites and promoted the repair of the mucosal epithelium in young and aged mice. It also suppressed the expression of IL-1ß and TNF-α and increased keratin 1 and 5 expression in the irritated gingiva. Propolis suppressed an increase in IL-1ß and TNF-α upon stimulation with H2O2 in young and SA-ß-gal-expressing senescent human gingival fibroblasts (HGFs) cultures. CONCLUSIONS: Propolis may be effective for mucosal repair in gingival irritation as it suppresses the expression of proinflammatory cytokines and promotes keratin expression.

Periodontal Disease and Periodontal Disease-Related Bacteria Involved in the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia, and it exhibits pathological properties such as deposition of extracellular amyloid ß (Aß) and abnormally phosphorylated Tau in nerve cells and a decrease of synapses. Conventionally, drugs targeting Aß and its related molecules have been developed on the basis of the amyloid cascade hypothesis, but sufficient effects on the disease have not been obtained in past clinical trials. On the other hand, it has been pointed out that chronic inflammation and microbial infection in the brain may be involved in the pathogenesis of AD. Recently, attention has been focused on the relationship between the periodontopathic bacterium Porphylomonas gingivalis and AD. P. gingivalis and its toxins have been detected in autopsy brain tissues from patients with AD. In addition, pathological conditions of AD are formed or exacerbated in mice infected with P. gingivalis. Compounds that target the toxins of P. gingivalis ameliorate the pathogenesis of AD triggered by P. gingivalis infection. These findings indicate that the pathological condition of AD may be regulated by controlling the bacteria in the oral cavity and the body. In the current aging society, the importance of oral and periodontal care for preventing the onset of AD will increase.