Electrophysiological properties of AQP6 in mouse parotid acinar cells

Salivary gland acinar cells secrete large amounts of water and electrolytes, where aquaporins (AQPs) are thought to be involved in the secretion. In the present study, we investigated expression/localization of AQP6, and the anion transporting properties of AQP6 in mouse parotid acinar cells. RT-PCR, western blotting and immunohistochemical analyses revealed expression of AQP6 in acinar cells, localized in apical membrane. Voltage ramp from -100 mV to +100 mV at a holding potential of -60 mV elicited outwardlyrectifying currents, in the presence of extracellular Cl- channel blockers and intracellular solution with 150 mM Cs+. These outward currents were increased when extracellular Cl- was replaced by Br-, NO3-, I-, or SCN-, accompanying a negative shift of reversal potentials. The outward current was enhanced by extracellular Hg2+. These results were consistent with the biophysical properties of transfected AQP6 oocytes or HEK cells, which indicate that the AQP6 channel is functionally expressed in parotid acinar cells, and suggest that AQP6 contributes to secretion of anions in parotid acinar cells

Temporal Expression Patterns of Clock Genes and Aquaporin 5/Anoctamin 1 in Rat Submandibular Gland Cells

Circadian rhythms are essential for health and regulate various physiological functions. These rhythms are regulated by a negative-feedback loop involving clock genes in the suprachiasmatic nucleus (SCN) and peripheral tissues. The rate of secretion of salivary substances, ions, and water follows a circadian rhythm, however, the relationship between the molecular mechanism of salivary secretion and peripheral circadian rhythm is not yet clear. Anoctamin 1 (ANO1, also known as TMEM16A) and Aquaporin 5 (AQP5) play an important role in the transport of ions and water in the submandibular glands (SGs). We examined the interaction between the rhythmic expression pattern of the clock genes, Ano1 and Aqp5, in rat whole SGs as well as isolated acinar and ductal cells. Circadian rhythmic expression for Bmal1, Per1, Per2, Clock, Cry1, Cry2, Rorα, and Rev-erbα mRNAs, also called the clock genes, was observed in rat SGs by semi-quantitative RT-PCR analysis. We also observed rhythmic patterns in Ano1 and Aqp5 mRNA expression. The expression of ANO1 protein also showed circadian rhythm, as confirmed by western blot analysis. We could not observe any time delay between the peak expression of ANO1 protein and its mRNA. Expression levels of the clock gene mRNAs in the ductal cells was higher than that in acinar cells, however, rhythmic oscillations were observed in both. Our results suggest that SGs have peripheral clocks, and rhythmic expressions of Ano1 and Aqp5 along with the clock genes, may play an important role in the circadian regulation of salivary secretion

Impact of employment on the elderly in a super-aging society during the COVID-19 pandemic in Japan

Abstract Employment of the elderly is gaining importance in Japan’s super-aging society. However, investigating the role of employment on the health of the elderly population during the coronavirus disease 2019 (COVID-19) pandemic, wherein they were susceptible, is necessary. We aimed to investigate whether the presence or absence of employment affected motor and cognitive functions in the elderly during the COVID-19 pandemic. The study involved 144 individuals aged ≥ 65 years who participated in the medical examination project from August to September 2021. The participants were divided into employed and non-employed groups. The motor function was evaluated by determining the walking speed, skeletal muscle mass, 2-step test, and bone density. Cognitive function was evaluated using the Mini Mental State Examination and Trail Making Test-A/B (TMT-A/B). For statistical examination, univariate analysis and logistic regression analysis were performed using significantly differential variables. Out of the 144 participants, 33 (22.9%) and 111 (77.1%) were in the employed and non-employed groups, respectively. TMT-A had an odds ratio of 0.96 (95% confidence interval 0.94–0.99) and was an independent factor in the employed group. In conclusion, the attention function was significantly higher in the employed group

Associations between depressive symptoms and geriatric syndromes in community-dwelling older adults in Japan: A cross-sectional study

It is estimated that 7.2% of community-dwelling older adults worldwide have major depression. Therefore, this study aimed to investigate the relationship between geriatric syndromes and depressive symptoms. Data were obtained from the Kaizuka Dementia Prevention Study 2018 and 2019, which was a community-based health check conducted in collaboration with the Osaka Kawasaki Rehabilitation University (Kaizuka City Office) and Cognitive Reserve Research Center in Osaka, Japan. The participants comprised 363 older adults (mean age 73.6 ± 6.6 years; women = 75.8%) who participated in a community-based health check. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). Depressive symptoms were defined as a GDS-15 score of ≥ 5. Furthermore, geriatric syndromes in participants—such as frailty, sarcopenia, and locomotive syndrome—were assessed. There was a 28.1% prevalence of depressive symptoms. In a logistic regression analysis with depressive symptoms as the dependent variable, both pre-frailty (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.09–3.01) and frailty (OR 5.45, 95% CI 2.23–13.31) were found to be significantly higher in the depressive group. There were no significant differences in sarcopenia and locomotive syndrome between the depressive groups. Our findings suggest that depressive symptoms are associated with frailty and pre-frailty in community-dwelling older adults in Japan. Physical frailty should be evaluated in depressed individuals and may contribute to the prioritization of clinical evaluation of geriatric syndromes

High pH-Sensitive Store-Operated Ca2+ Entry Mediated by Ca2+ Release-Activated Ca2+ Channels in Rat Odontoblasts

Odontoblasts play a crucial role in dentin formation and sensory transduction following the application of stimuli to the dentin surface. Various exogenous and endogenous stimuli elicit an increase in the intracellular free calcium concentration ([Ca2+]i) in odontoblasts, which is mediated by Ca2+ release from intracellular Ca2+ stores and/or Ca2+ influx from the extracellular medium. In a previous study, we demonstrated that the depletion of Ca2+ stores in odontoblasts activated store-operated Ca2+ entry (SOCE), a Ca2+ influx pathway. However, the precise biophysical and pharmacological properties of SOCE in odontoblasts have remained unclear. In the present study, we examined the functional expression and pharmacological properties of Ca2+ release-activated Ca2+ (CRAC) channels that mediate SOCE and evaluated the alkali sensitivity of SOCE in rat odontoblasts. In the absence of extracellular Ca2+, treatment with thapsigargin (TG), a sarco/endoplasmic reticulum Ca2+-ATPase inhibitor, induced an increase in [Ca2+]i. After [Ca2+]i returned to near-resting levels, the subsequent application of 2.5 mM extracellular Ca2+ resulted in an increase in [Ca2+]i which is a typical of SOCE activation. Additionally, application of 2-methylthioadenosine diphosphate trisodium salt (2-MeSADP), a P2Y1,12,13 receptor agonist, or carbachol (CCh), a muscarinic cholinergic receptor agonist, in the absence of extracellular Ca2+, induced a transient increase in [Ca2+]i. The subsequent addition of extracellular Ca2+ resulted in significantly higher [Ca2+]i in 2-MeSADP- or CCh-treated odontoblasts than in untreated cells. SOCE, that is activated by addition of extracellular Ca2+ in the TG pretreated odontoblasts was then suppressed by Synta66, BTP2, or lanthanum, which are CRAC channel inhibitors. Treatment with an alkaline solution enhanced SOCE, while treatment with HC030031, a TRPA1 channel antagonist, inhibited it. The amplitude of SOCE at pH 9 in the presence of HC030031 was higher than that at pH 7.4 in the absence of HC030031. These findings indicate that CRAC channel-mediated alkali-sensitive SOCE occurs in odontoblasts. SOCE is mediated by P2Y and muscarinic-cholinergic receptors, which are activated by endogenous ligands in odontoblasts

Association between Bone-Related Physiological Substances and Oral Function in Community-Dwelling Older People

Background: Oral dysfunction is related to long-term cares including activities of daily living. The objective of this study was to determine the association between oral function and the bone-related physiological substances osteocalcin (OC) and insulin-like growth factor-1 (IGF-1). Methods: The study participants were 139 community-dwelling older people in Japan. Evaluation of oral dysfunction was based on subjective judgment by each participant. Blood analysis included OC, IGF-1, and albumin. Results: Univariate and multiple logistic analyses showed that IGF-1 was significantly associated with a “decline in masticatory function” (p = 0.0074 and p = 0.0308, respectively). Receiver operating characteristic curve analysis of IGF-1 levels revealed a threshold score of 108 ng/mL (p < 0.01) for discriminating a “decline in masticatory function”. Logistic regression analysis revealed that participants with an IGF-1 level ≤108 ng/mL had an odds ratio of 4.31 (p < 0.05) for a “decline in masticatory function”. No significant association was found between the OC level and oral dysfunction. Conclusions: These results suggest a possible relationship between lower serum IGF-1 levels and a decline in masticatory dysfunction in community-dwelling older people