Mitochondrial Calcium Uniporter (MCU) is Involved in an Ischemic Postconditioning Effect Against Ischemic Reperfusion Brain Injury in Mice.

The phenomenon of ischemic postconditioning (PostC) is known to be neuroprotective against ischemic reperfusion (I/R) injury. One of the key processes in PostC is the opening of the mitochondrial ATP-dependent potassium (mito-KATP) channel and depolarization of the mitochondrial membrane, triggering the release of calcium ions from mitochondria through low-conductance opening of the mitochondrial permeability transition pore. Mitochondrial calcium uniporter (MCU) is known as a highly sensitive transporter for the uptake of Ca2+ present on the inner mitochondrial membrane. The MCU has attracted attention as a new target for treatment in diseases, such as neurodegenerative diseases, cancer, and ischemic stroke. We considered that the MCU may be involved in PostC and trigger its mechanisms. This research used the whole-cell patch-clamp technique on hippocampal CA1 pyramidal cells from C57BL mice and measured changes in spontaneous excitatory post-synaptic currents (sEPSCs), intracellular Ca2+ concentration, mitochondrial membrane potential, and N-methyl-D-aspartate receptor (NMDAR) currents under inhibition of MCU by ruthenium red 265 (Ru265) in PostC. Inhibition of MCU increased the occurrence of sEPSCs (p = 0.014), NMDAR currents (p < 0.001), intracellular Ca2+ concentration (p < 0.001), and dead cells (p < 0.001) significantly after reperfusion, reflecting removal of the neuroprotective effects in PostC. Moreover, mitochondrial depolarization in PostC with Ru265 was weakened, compared to PostC (p = 0.004). These results suggest that MCU affects mitochondrial depolarization in PostC to suppress NMDAR over-activation and prevent elevation of intracellular Ca2+ concentrations against I/R injury.

Complete dentures associated with frailty among edentulous older Japanese people: A prospective analysis.

OBJECTIVE: This study aimed to explore the cross-sectional and prospective associations between self-reported functionality of complete dentures (FCD), satisfaction with complete dentures (SCD) and the ability to chew hard food (ACHF) on the one hand and the frailty index (FI) on the other hand among edentulous community-dwelling older Japanese people. METHODS: The study examined 770 edentulous participants of the Nihon University Japanese Longitudinal Study of Aging. The self-reported FCD, SCD and ability to chew six groups of food (from hardest to softest) with complete dentures were the independent variables at the baseline. The FI was computed including 40 deficits as the dependent variable at the baseline and 4 years later. Cross-sectional and prospective generalized linear regression models were fitted controlling for age, gender, marital status, education, working status and area of residence. RESULTS: The use of non-functional complete dentures and dissatisfaction with complete dentures were both associated with a higher FI cross-sectionally (3.9% [95% CI 2.2-5.6] and 3.2% [95% CI 1.5-4.9], respectively) and prospectively (3.9% [95% CI 2.0-6.0] and 3.3% [95% CI 1.3-5.3], respectively). Regarding the ability to chew, a higher FI at baseline was observed among those able to chew food of Group 2 (1.9%, [95% CI 0.1-3.7]) and Groups 4-6 (1.9%, [95% CI 0.1-3.7]), and a progressive increment in the FI, as the participants reported being able to chew softer groups of food at the follow-up (Group 2: 2.2% [95% CI 0.05-4.3]; Group 3: 3.6% [95% CI 1.2-6.0]; and Groups 4-6: 3.4 [95% CI 0.7-6.1]). CONCLUSION: Self-reported use of non-functional complete dentures, dissatisfaction with dentures and a reduced ACHF with complete dentures were associated with a higher FI both cross-sectionally and prospectively.

Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines.

BACKGROUND: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-α (TNF-α) expression in granulocyte-macrophage colony-stimulating factor-induced macrophages (GM-CSF MΦ) and the TNF-α expression ratio in GM-CSF MΦ/M-CSF MΦ (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. METHODS: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. RESULTS: Our results of co-culture experiments showed that GM-CSF MΦ affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1α and TNF-α. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. LIMITATIONS: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. CONCLUSIONS: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF MΦ in individuals with ASD on neurons, mediated by interleukin-1α and TNF-α. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology.

Falls among community-dwelling older adults in the Philippines and Viet Nam: Results from nationally representative samples.

Falls are a significant public health issue globally. However, studies with nationally representative samples have yet to be done to understand falls among older adults in the Philippines and Viet Nam. Using a biopsychosocial perspective, this study investigated the prevalence of falls and their associated factors among community-dwelling older adults in these countries. Cross-sectional data were drawn from the baseline survey of the Longitudinal Study of Ageing and Health in the Philippines (2018, N = 4,606) and the Longitudinal Study of Ageing and Health in Viet Nam (2018, N = 4,378). The outcome variables were any falls in the past year. Independent variables included sociodemographic factors (age, sex, education, living in urban areas, living alone, social network size), biophysical factors (vision, chronic conditions, functional impairments, pain locations, insomnia symptoms, sleep medications, grip strength, walking speed, postural control), and psychological factors (depressive symptoms). Descriptive analysis and logistic regression analysis were used to analyze the data. The results showed that 17.7 % and 7.3 % of older Filipino and Vietnamese adults fell in the year before the study. Significant factors associated with the odds of any falls among Filipino older adults were having a higher level of education, living in urban areas, living with others, experiencing more functional impairments, reporting one or more pain locations, and having poor grip strength. In Viet Nam, having more chronic conditions, experiencing more functional impairments, and reporting two or more pain locations were found to be associated with higher odds of any falls. The population in the Philippines and Viet Nam is aging rapidly. Findings from this study are timely in identifying at-risk individuals and preparing for effective fall prevention strategies.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45-p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans.

Prevalence, Awareness, Treatment, and Control of Hypertension Among Older Adults in the Philippines.

BACKGROUND: Little is known about the current prevalence and management of hypertension among older Filipinos. To address this gap, we examined the prevalence, awareness, treatment, and control of hypertension, as well as their correlates, among older Filipinos. METHODS: We analyzed a nationally representative survey of Filipinos aged 60 years and older (N = 5 985) in the Philippines. Blood pressure (BP) measurements were taken using a digital BP apparatus. People with hypertension included those with a systolic BP ≥ 140 mmHg or a diastolic BP ≥ 90 mmHg, or those who reported current use of antihypertensive medication. People with undiagnosed hypertension were those who had measured hypertension but had not been diagnosed by a doctor as having hypertension, while people with untreated hypertension were those who had measured hypertension but not taking medication. Among those who were taking antihypertensive medication, respondents with measured hypertension were considered to have uncontrolled BP. RESULTS: Results showed that 69.1% of older Filipinos had hypertension, but only 61.6% of people with hypertension were aware of their hypertension and 51.5% were untreated. Sociodemographic factors, such as age, sex, education, and living arrangements, were significantly associated with hypertension prevalence, hypertension awareness, lack of treatment for hypertension, and/or suboptimal BP control. CONCLUSION: We observed a high prevalence of hypertension among older Filipinos and a relatively low level of awareness and treatment of hypertension among them. While there are government efforts to address the growing prevalence of hypertension in the country, more efforts should be made to bring these government programs to older Filipinos.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglia Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglia BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administration of doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological functions; this was not observed when BDNF was normalized from a later age (p45-p50). To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible substitute for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. Thus, microglia BDNF might regulate sociability and mPFC maturation in mice during the juvenile period. Furthermore, childhood experiences in humans may be related to BDNF secretion from macrophages.

Sex differences in the psychometric properties of the Center for Epidemiological Studies-Depression (CES-D) Scale in older Filipinos.

The literature has yet to fully account for sex differences in the symptomatology and measurement of depressive symptoms, especially in developing settings like the Philippines. Thus, we established the factor structure and assessed the reliability of the 11-item version of the Center for Epidemiological Studies-Depression (CES-D) Scale for assessing depressive symptoms in older Filipino men and women. Using cross-sectional data from 5,209 community-dwelling Filipinos aged 60 and above from a nationally representative survey, Confirmatory Factor Analysis (CFA) and methods in Item Response Theory (IRT) were applied to provide complementary insights into the properties of the scale and its individual items. CFA supported the multidimensionality of the scale. The scale is also sex-invariant, but the relationship between the subfactors and the higher-order factor may differ between men and women. In addition, findings from IRT analysis confirmed the overall utility of the CES-D scale, but positively stated items were found to be internally inconsistent with the rest of the scale. The scale is desirably informative for assessing more severe symptoms, although sex differences were found in the precision of individual items. In general, the 11-item CES-D Scale is an adequate multidimensional tool for assessing moderate to severe depressive symptoms in the older population, especially in older men.

Nutritional Status Predicts Injurious Falls Among Community-Dwelling Older Adults: Does Sex Matter?

The association of poor nutritional status with falls-related injuries other than fractures is unclear. Although there are sex differences in poor nutritional status and the rate of falls-related injuries, whether the impacts of poor nutritional status on falls-related injuries differ by sex is unclear. We investigated whether baseline poor nutritional status predicted injurious falls, fall-related minor injuries, and fractures at 3-year follow-up and whether these relationships differed by sex among community-dwelling older adults (N = 3257). We found that being at risk of malnutrition at baseline significantly predicted injurious falls but not minor injuries and fractures at follow-up. Compared to older males at risk of malnutrition at baseline, females at risk of malnutrition were significantly more likely to have injurious falls and minor injuries later. Being at risk of malnutrition predicted injurious falls, especially among older females. Regular nutritional screenings among older females should be implemented to provide prompt interventions against falls.

Subjective Well-Being and Active Life Expectancy in Japan: Evidence From a Longitudinal Study.

Background and Objectives: Existing research has suggested that older adults in Japan enjoy phenomenal physical health status, but they have poor subjective well-being (SWB). Limited empirical evidence exists, however, on how physical health and SWB intersect and are linked to the lives of older men and women in Japan. Using the concept of health expectancy, this study examines the role of SWB, as measured by life satisfaction, in the mortality and morbidity experiences of Japanese adults aged 65 years and older. Research Design and Methods: We used the nationally representative Nihon University Japanese Longitudinal Study of Aging, 1999-2009. Our measurement of morbidity is disability, based on difficulty in activities in daily living (ADLs) and instrumental ADLs. We use the Interpolation of Markov Chains approach to compute life expectancy (LE), LE without disability (active LE), and LE with differing severity of disability for those who are satisfied with life and for those who are not. Results: We documented significant differences in LE and active LE by the state of life satisfaction among older adults in Japan. Men and women who are satisfied with life are expected to live longer and spend more years without having disability compared to those who are not satisfied. We found no differences in the length of life with disability of differing severity by the state of life satisfaction. Discussion and Implications: Our results highlight the important role of SWB at older ages in Japan, because it is directly related to the physical health of its aging population. Fully understanding the health of the older population requires research that focuses on both objective and subjective dimensions of well-being.

Serotonergic current responses of neurons in rat oculomotor neural integrators.

The prepositus hypoglossi nucleus (PHN) and the interstitial nucleus of Cajal (INC) are involved in controlling horizontal and vertical gaze, respectively. Previous studies have shown that PHN neurons exhibit depolarized or hyperpolarized responses to serotonin (5-hydroxytryptamine, 5-HT). However, serotonergic modulation of INC neurons has not been examined. Furthermore, the relationship between 5-HT-induced responses and neuron types based on neurotransmitter phenotypes has not been clarified. In this study, we investigated 5-HT-induced current responses in PHN and INC neurons and the distributions of distinct current responses in different neuron types, using whole cell recordings of wild-type and transgenic rat brain stem slices. Local application of 5-HT to the cell soma confirmed that slow inward (SI) and slow outward (SO) currents were mediated by 5-HT2 and 5-HT1A receptors, respectively. Furthermore, fast inward (FI) currents that were mediated by 5-HT3 receptors were observed. These three current responses were observed in both PHN and INC neurons. Analyses of the distributions of the three current responses revealed that fluorescently identified glutamatergic and inhibitory neurons in the PHN showed high proportions of SI and SO currents, respectively, whereas glutamatergic and inhibitory neurons in the INC showed mainly SO currents. When PHN and INC neurons were characterized on the basis of firing patterns, the proportions of the currents depended on the firing patterns. The different distributions of 5-HT-induced currents suggest distinct serotonergic modulation modes specific to horizontal and vertical gaze control.NEW & NOTEWORTHY Serotonergic modulation of vertical gaze control (interstitial nucleus of Cajal, INC) is less understood than that of horizontal gaze control (prepositus hypoglossal nucleus, PHN). Here, we report 5-HT-induced fast inward currents in addition to the previously reported slow inward and outward currents. The distributions of these currents in INC neurons based on neurotransmitter phenotypes differ from those in PHN neurons. These results suggest distinct serotonergic modulation modes in horizontal and vertical gaze control centers.

Juvenile social isolation immediately affects the synaptic activity and firing property of fast-spiking parvalbumin-expressing interneuron subtype in mouse medial prefrontal cortex.

A lack of juvenile social experience causes various behavioral impairments and brain dysfunction, especially in the medial prefrontal cortex (mPFC). Our previous studies revealed that juvenile social isolation for 2 weeks immediately after weaning affects the synaptic inputs and intrinsic excitability of fast-spiking parvalbumin-expressing (FSPV) interneurons as well as a specific type of layer 5 (L5) pyramidal cells, which we termed prominent h-current (PH) cells, in the mPFC. However, since these changes were observed at the adult age of postnatal day 65 (P65), the primary cause of these changes to neurons immediately after juvenile social isolation (postnatal day 35) remains unknown. Here, we investigated the immediate effects of juvenile social isolation on the excitability and synaptic inputs of PH pyramidal cells and FSPV interneurons at P35 using whole-cell patch-clamp recording. We observed that excitatory inputs to FSPV interneurons increased immediately after juvenile social isolation. We also found that juvenile social isolation increases the firing reactivity of a subtype of FSPV interneurons, whereas only a fractional effect was detected in PH pyramidal cells. These findings suggest that juvenile social isolation primarily disturbs the developmental rebuilding of circuits involving FSPV interneurons and eventually affects the circuits involving PH pyramidal cells in adulthood.

Neural Subtype-dependent Cholinergic Modulation of Neural Activities by Activation of Muscarinic 2 Receptors and G Protein-activated Inwardly Rectifying Potassium Channel in Rat Periaqueductal Gray Neurons.

Acetylcholine plays a pivotal role in the regulation of functions such as pain and the sleep and wake cycle by modulating neural activities of the ventrolateral periaqueductal gray (vlPAG). Electrophysiological studies have shown that cholinergic effects are inconsistent among recorded neurons, particularly in the depolarization and hyperpolarization of the resting membrane potential (RMP). This discrepancy may be due to the neural subtype-dependent cholinergic modulation of the RMP. To examine this possibility, we performed whole-cell patch-clamp recordings from subtype-identified neurons using vesicular GABA transporter (VGAT)-Venus × ChAT-TdTomato rats and elucidated cellular mechanisms of cholinergic effects on the RMP. The application of carbachol hyperpolarized the RMP of cholinergic neurons in a dose-dependent manner but had much less of an effect on other neural subtypes, including GABAergic/glycinergic and glutamatergic neurons. Cholinergic hyperpolarization was accompanied by a decrease in input resistance. These cholinergic effects were blocked by AF-DX384 or gallamine and were mimicked by arecaidine but-2-ynyl ester tosylate, suggesting that the carbachol-induced hyperpolarization of the RMP in cholinergic neurons is mediated via M2 receptors. Tertiapin suppressed the carbachol-induced G protein-activated inwardly rectifying potassium channel (GIRK) currents and hyperpolarization of the RMP in cholinergic neurons. Intracellular application of GDP-ß-S blocked the carbachol-induced hyperpolarization of the RMP. Neostigmine slowly hyperpolarized the RMP in cholinergic neurons. These results suggest that neural firing of vlPAG cholinergic neurons is suppressed by GIRK currents induced via M2 receptor activation, and this negative feedback regulation of cholinergic neuronal activities can be induced by acetylcholine, which is intrinsically released in the vlPAG.

Is there compression or expansion of morbidity in the Philippines?

AIMS: This study contributes to previous initiatives examining healthy and active aging in the Philippines. METHODS: We employed the Sullivan method to calculate healthy life expectancy (HLE) and active life expectancy (ALE) using the 2007 Philippine Survey on Aging and the 2018 Longitudinal Study of Ageing and Health. We compared the estimates at two time points, providing evidence of change over time. RESULTS: There was no statistically significant change in the relative proportion of HLE over time for both sexes, suggesting dynamic equilibrium. For men, the increase in life expectancy was mainly an increase in unhealthy state (UHLE). The slight increases in HLE for all ages were not statistically significant. The differences in relative increase in HLE were not statistically significant. HLE for women increased over time, with statistically significant increases at ages 60 and 70 years. ALE declined in all age groups for both sexes, but the decline was statistically significant only among women in their 60s and 70s. There was also a statistically significant decline in the proportion of remaining life in an active state for all ages among both men and women, suggesting an expansion of morbidity. CONCLUSIONS: Findings suggest no evidence of compression of morbidity in the Philippines from 2007 to 2018. The HLE results suggest a dynamic equilibrium, while ALE results indicate an expansion of morbidity. The findings emphasize the need for the government to promote life course interventions that foster healthy choices and conduct further research to understand the factors influencing longevity and active aging in the Philippines. Geriatr Gerontol Int 2022; 22: 511-515.

Older Adults' Loneliness and Social Relationships in the Philippines: Comparison Between Rural and Urban Contexts.

This study compared patterns of association between social relationship measures and levels of loneliness for rural and urban older adults in the Philippines. We analyzed social relationship measures and loneliness scores (UCLA Three-Item Loneliness Scale) of a nationally representative sample of Filipino adults 60 years and older in the baseline survey of the 2018 Longitudinal Study of Ageing and Health in the Philippines (LSAHP) (n=4,704). The loneliness score was slightly higher for rural older adults (5.8) than for their urban counterparts (5.1; p=.0001). A significantly larger proportion of older adults in rural areas (12.7%) lived alone than in urban areas (5.4%; p=.0008). The overall pattern of association between social relationship measures and loneliness scores for the two groups was mostly similar. For both groups, living alone, having less active social involvement, and seeing friends less frequently were related to higher levels of loneliness. Poorer subjective financial well-being (e.g., the perception of considerable difficulty in making ends meet) was also significantly associated with higher loneliness scores. These findings suggest that the prevention of loneliness for older adults in countries in the early stages of population aging such as the Philippines requires a broad range of public health initiatives.

Behavioral and Immunohistochemical Evidence for Suppressive Effects of Goshajinkigan on Salicylate-Induced Tinnitus in Rats.

Many people are affected by tinnitus, a sensation of ringing in the ear despite the absence of external sound. Goshajinkigan (GJG) is one of the formulations of Japanese traditional herbal medicine and is prescribed for the palliative treatment of patients with tinnitus. Although GJG is clinically effective in these patients, its behavioral effects and the underlying neuroanatomical substrate have not been modeled in animals. We modeled tinnitus using salicylate-treated rats, demonstrated the effectiveness of GJG on tinnitus, and examined the underlying neuronal substrate with c-Fos expression. Intraperitoneal injection of sodium salicylate (400 mg/kg) into rats for three consecutive days significantly increased false positive scores, which were used to assess tinnitus behavior. When GJG was orally administered one hour after each salicylate injection, the increase in tinnitus behavior was suppressed. The analysis of c-Fos expression in auditory-related brain areas revealed that GJG significantly reduced the salicylate-induced increase in the number of c-Fos-expressing cells in the auditory cortices, inferior colliculus, and dorsal cochlear nucleus. These results suggest a suppressive effect of GJG on salicylate-induced tinnitus in animal models.

Melatonin-Induced Postconditioning Suppresses NMDA Receptor through Opening of the Mitochondrial Permeability Transition Pore via Melatonin Receptor in Mouse Neurons.

Mitochondrial membrane potential regulation through the mitochondrial permeability transition pore (mPTP) is reportedly involved in the ischemic postconditioning (PostC) phenomenon. Melatonin is an endogenous hormone that regulates circadian rhythms. Its neuroprotective effects via mitochondrial melatonin receptors (MTs) have recently attracted attention. However, details of the neuroprotective mechanisms associated with PostC have not been clarified. Using hippocampal CA1 pyramidal cells from C57BL mice, we studied the involvement of MTs and the mPTP in melatonin-induced PostC mechanisms similar to those of ischemic PostC. We measured changes in spontaneous excitatory postsynaptic currents (sEPSCs), intracellular calcium concentration, mitochondrial membrane potential, and N-methyl-D-aspartate receptor (NMDAR) currents after ischemic challenge, using the whole-cell patch-clamp technique. Melatonin significantly suppressed increases in sEPSCs and intracellular calcium concentrations. The NMDAR currents were significantly suppressed by melatonin and the MT agonist, ramelteon. However, this suppressive effect was abolished by the mPTP inhibitor, cyclosporine A, and the MT antagonist, luzindole. Furthermore, both melatonin and ramelteon potentiated depolarization of mitochondrial membrane potentials, and luzindole suppressed depolarization of mitochondrial membrane potentials. This study suggests that melatonin-induced PostC via MTs suppressed the NMDAR that was induced by partial depolarization of mitochondrial membrane potential by opening the mPTP, reducing excessive release of glutamate and inducing neuroprotection against ischemia-reperfusion injury.

Factors Associated With High Rates of Depressive Symptomatology in Older People in Vietnam.

OBJECTIVES: This study aimed to identify the prevalence and correlates of depressive symptomatology among Vietnamese older people. METHOD: We used baseline survey data collected in 2018 from the Longitudinal Study of Ageing and Health in Vietnam (LSAHV) conducted across seven regions and comprising 6,050 people aged 60 years and over of whom 4962 completed the brief 11-item Center for Epidemiological Studies-Depression (CES-D) scale. Clinically significant depressive symptomatology was a CES-D score of 8.8 or higher. The association between demographic, physical, and mental factors with depressive symptomatology was examined using univariate and multivariable logistic regression. RESULTS: The prevalence of depressive symptomatology was 31.3% (95% CI 29.8% - 32.9%). Depressive symptomatology was highest among people living in the Central Coast region (46.8%, 95% CI 44.5% - 49.2%). Factors associated with depressive symptomatology from the multivariable model included female sex (OR 1.3, 95% CI: 1.1-1.6), rural residence (OR 1.4, 95%CI: 1.1-1.7), not having a partner (OR 1.6, 95% CI: 1.3-1.9), low income (OR 1.8, 95% CI: 1.5-2.1), and health-limitations on activities (OR 1.3, 95% CI: 1.1-1.6). Poorer self-rated mental health (OR 2.1, 95% CI:1.8-2.5) or general health status (OR 1.5, 95% CI: 1.3-1.9) was associated with a higher prevalence of depressive symptomatology, as was poorer function with respect to different activities of daily living, and dissatisfaction with current life (OR 6.1, 95% CI: 4.4-8.4). CONCLUSIONS: Depressive symptomatology was frequent among older Vietnamese. Efforts to improve mental health in older persons in Vietnam, including prevention, early intervention and better medical care, appear warranted.

Changes in Health Expectancy for Older Adults in Japan: Results from Two Longitudinal Surveys.

BACKGROUND: Although there is evidence of improvements in health expectancy among the Japanese population, existing estimates are based on the prevalence of morbidity taken from cross-sectional survey data. OBJECTIVES: This study employed a multistate life table approach to compute incidence-based health expectancy measures, namely active and inactive life expectancy (LE), for two longitudinal survey cohorts from 1990 to 2009. METHODS: This study used data from two longitudinal surveys of older adults in Japan: the National Survey of the Japanese Elderly (1990-1999) and the Nihon University Japanese Longitudinal Study of Aging (1999-2009). We employed the Interpolation of Markov Chains technique to compute the number of years at age 65 years to be spent with and without difficulty in performing activities of daily living (ADLs) or instrumental ADLs. RESULTS: We documented significant increases in active LE for men and women at age 65 years over the 10-year study period. There were significant changes in total LE for men and in the percentage of active life for women. Inactive LE did not significantly change across the two survey cohorts during the study period. CONCLUSIONS: Our results show that the health status of older adults in Japan has largely improved over the 10-year study period, with increases in both the duration of life and time spent in an active state. This finding offers evidence of compression of morbidity among older men and women in Japan.

Ischemic Postconditioning Reduces NMDA Receptor Currents Through the Opening of the Mitochondrial Permeability Transition Pore and KATP Channel in Mouse Neurons.

Ischemic postconditioning (PostC) is known to reduce cerebral ischemia/reperfusion (I/R) injury; however, whether the opening of mitochondrial ATP-dependent potassium (mito-KATP) channels and mitochondrial permeability transition pore (mPTP) cause the depolarization of the mitochondrial membrane that remains unknown. We examined the involvement of the mito-KATP channel and the mPTP in the PostC mechanism. Ischemic PostC consisted of three cycles of 15 s reperfusion and 15 s re-ischemia, and was started 30 s after the 7.5 min ischemic load. We recorded N-methyl-D-aspartate receptors (NMDAR)-mediated currents and measured cytosolic Ca2+ concentrations, and mitochondrial membrane potentials in mouse hippocampal pyramidal neurons. Both ischemic PostC and the application of a mito-KATP channel opener, diazoxide, reduced NMDAR-mediated currents, and suppressed cytosolic Ca2+ elevations during the early reperfusion period. An mPTP blocker, cyclosporine A, abolished the reducing effect of PostC on NMDAR currents. Furthermore, both ischemic PostC and the application of diazoxide potentiated the depolarization of the mitochondrial membrane potential. These results indicate that ischemic PostC suppresses Ca2+ influx into the cytoplasm by reducing NMDAR-mediated currents through mPTP opening. The present study suggests that depolarization of the mitochondrial membrane potential by opening of the mito-KATP channel is essential to the mechanism of PostC in neuroprotection against anoxic injury.