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.

Noradrenergic current responses of neurons in rat oculomotor neural integrators.

The prepositus hypoglossi nucleus (PHN) and the interstitial nucleus of Cajal (INC) are involved in the control of horizontal and vertical gaze, respectively. A previous study showed that PHN neurons exhibit depolarized or hyperpolarized responses to noradrenaline (NA). However, the adrenoceptor types that participate in NA-induced responses and the effects of NA on INC neurons have not yet been investigated. Furthermore, the relationship between NA-induced responses and neuron types defined by neurotransmitter phenotypes has not been determined. In this study, we investigated NA-induced current responses in PHN and INC neurons and the relationships between these responses and neuron types using whole cell recordings in wild-type and transgenic rat brainstem slices. Local application of NA to the cell soma induced slow inward (SI) and slow outward (SO) currents that were mainly mediated by α1 and α2 adrenoceptors, respectively. These current responses were observed in both PHN and INC neurons, although the proportion of INC neurons that responded to NA was low. Analyses of the distributions of the current responses revealed that in the PHN, all fluorescently identified inhibitory neurons exhibited SI currents, whereas glutamatergic and cholinergic neurons exhibited both SI and SO currents. In the INC, glutamatergic and inhibitory neurons preferentially exhibited SI and SO currents, respectively. When the PHN and INC neurons were characterized by their firing pattern, we found that the proportions of the currents depended on their firing pattern. These results suggest that various modes of noradrenergic modulation in horizontal and vertical neural integrators are dependent on neuron type.NEW & NOTEWORTHY Noradrenergic modulation of oculomotor neural integrators involved in gaze control has not been elucidated. Here, we report that noradrenaline (NA)-induced slow inward (SI) and outward (SO) currents are mediated mainly by α1 and α2 adrenoceptors in neurons that participate in horizontal and vertical gaze control. The NA-induced current responses differed depending on the neurotransmitter phenotype and firing pattern. These results suggest various modes of noradrenergic modulation in horizontal and vertical integrator neurons.

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.

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.

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.

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.

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.

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.

Are Religiosity and Spirituality Related to Self-Reported Health Expectancy? An Analysis of the European Values Survey.

Research on religiosity and health has generally focussed on the United States, and outcomes of health or mortality but not both. Using the European Values Survey 2008, we examined cross-sectional associations between four dimensions of religiosity/spirituality: attendance, private prayer, importance of religion, belief in God; and healthy life expectancy (HLE) based on self-reported health across 47 European countries (n = 65,303 individuals). Greater levels of private prayer, importance of religion and belief in God, at a country level, were associated with lower HLE at age 20, after adjustment for confounders, but only in women. The findings may explain HLE inequalities between European countries.

Differential regulation of medium spiny and cholinergic neurons in the nucleus accumbens core by the insular and medial prefrontal cortices in the rat.

The nucleus accumbens (NAc) receives cortical projections principally from the insular cortex (IC) and medial prefrontal cortex (mPFC). Among NAc neurons, cholinergic interneurons (ChNs) regulate the activities of medium spiny neurons (MSNs), which make up ~ 95% of NAc neurons, by modulating their firing and synaptic properties. However, little is known about the synaptic mechanisms, including their cell-type-dependent corticoaccumbal projection properties and cholinergic effects on the NAc core. Here, we performed whole-cell patch-clamp recordings from NAc MSNs and ChNs in acute brain slice preparations obtained from rats that received an AAV5-hSyn-ChR2(H134R)-mCherry injection into the IC or mPFC. Light stimulation of IC or mPFC axons induced comparable phase-locked excitatory postsynaptic currents (EPSCs) in MSNs. On the other hand, ChNs showed consistent EPSCs evoked by light stimulation of mPFC axons, whereas light stimulation of IC axons evoked much smaller EPSCs, which often showed failure in ChNs. Light-evoked EPSCs were abolished by tetrodotoxin and were recovered by 4-aminopyridine, suggesting that corticoaccumbal projections monosynaptically induce EPSCs in MSNs and ChNs. Carbachol effectively suppressed the amplitude of EPSCs in MSNs and ChNs evoked by light stimulation of IC or mPFC axons and in ChNs evoked by stimulating mPFC axons. The carbachol-induced suppression was recovered by atropine or pirenzepine, while preapplication of gallamine, J104129, PD102807, or AF-DX384 did not block the carbachol-induced EPSC suppression. These results suggest that NAc MSNs and ChNs are differentially regulated by excitatory projections from the IC and mPFC and that these corticoaccumbal excitatory inputs are modulated by M1 receptor activation.

Distinct purinergic receptor-mediated currents of rat oculomotor integrator neurons characterized by different firing patterns.

The prepositus hypoglossi nucleus (PHN) and the interstitial nucleus of Cajal (INC) are oculomotor neural integrators involved in the control of horizontal and vertical gaze, respectively. We previously reported that local application of adenosine 5'-trisphosphate (ATP) to PHN neurons induced P2X receptor-mediated fast inward currents, P2Y receptor-mediated slow inward currents, and/or adenosine P1 receptor-mediated slow outward currents. In contrast to the findings on PHN neurons, the expression of functional purinergic receptors in INC neurons has not been examined. In this study, we investigated ATP-induced current responses in INC neurons and the distributions of the three current types across distinct firing patterns in PHN and INC neurons using whole cell recordings of rat brainstem slices. The application of ATP induced all three current types in INC neurons. Pharmacological analyses indicated that the fast inward and slow outward currents were mainly mediated by the P2X and P1 subtypes, respectively, corresponding to the receptor subtypes in PHN neurons. However, agonists of the P2Y subtype did not induce the slow inward current in INC neurons, suggesting that other subtypes or mechanisms are responsible for this current. Analysis of the distribution of the three current types in PHN and INC neurons revealed that the proportions of the currents were distinctly dependent on the firing patterns of PHN neurons whereas the proportion of the fast inward current was higher during all firing patterns of INC neurons. The different distributions of ATP-induced currents suggest distinct modes of purinergic modulation specific to horizontal and vertical integrators.NEW & NOTEWORTHY The roles of purinergic signaling on vertical (mediated by the interstitial nucleus of Cajal; INC) and horizontal (prepositus hypoglossal nucleus; PHN) gaze control are not understood. Here, we report three current types induced by ATP in INC neurons; the distribution of these current types across different types of INC neurons is different from that in PHN neurons. These results suggest distinct modes of purinergic modulation in horizontal and vertical gaze control centers.

Disasters and the Disablement Process framework: an analysis of the great east Japan earthquake and tsunami of 2011.

This study used the Disablement Process framework to examine how exposure to the great east Japan earthquake and tsunami on 11 March 2011 was related to elders' experiences of disability-that is, 'a gap between personal capability and environmental demand' (Verbrugge and Jette, 1994, p. 1). Data were derived from two waves (2009 and 2013) of the Nihon University Japanese Longitudinal Study of Aging, involving a representative sample of citizens aged 65 or more. Logistic regression was employed to model how the disaster was associated with the prevalence and incidence of disability. A significant relationship was documented between the two. Those impacted by the event exhibited greater odds of reporting a disability in 2013 and developing one between 2009 and 2013. Disasters destroy social infrastructure and disrupt daily life, widening the lacuna between the environment and personal resources. Given the increasing number of disasters, more policy attention should be directed to reducing their adverse consequences for health.

Does Religious Activity Distinguish the Mortality Experiences of Older Taiwanese? An Analysis Using Eighteen Years of Follow-Up Data.

This paper extends investigation of religiosity and longevity to Taiwan using a 1989 survey: N = 3849, aged 60+, with 18 years of follow-up. Religious activity is measured as worship and performance of rituals. A Gompertz regression, adjusted and non-adjusted for covariates and mediating factors, shows the hazard of dying is lower for the religiously active versus the non-active. Transformed into life table functions, a 60-year-old religiously active Taiwanese female lives more than 1 year longer than her non-religious counterpart, ceteris paribus. Mainland Chinese migrants are examined carefully because of unique religious and health characteristics. They live longer, but the religiosity gap is similar.

Years of life with and without limitation in physical function and in activities of daily living by body mass index among older adults.

BACKGROUND: While older adults with pre-obesity and Class I obesity have similar or lower mortality risk versus those with normal weight, a heavier body mass index (BMI) may not translate into more healthy life years. Utilizing longitudinal data on 3452 older (≥60 years) Singaporeans, we assessed the association between BMI and years of remaining life overall with and without limitation in physical function and in activities of daily living (ADLs). METHODS: Difficulty in any of nine tasks involving upper or lower extremities was considered as limitation in physical function, and health-related difficulty in any basic ADL or instrumental ADL as limitation in ADLs. We utilized multistate life tables, including BMI as a time-varying covariate. RESULTS: At age 60, life expectancy (LE) was similar for those with normal weight, pre-obesity and obesity. However, those with obesity, versus normal weight, had 6.3 [95% confidence interval: 3.4-9.2] more years with limitation in physical function and 4.9 [3.4-6.5] less years without limitation in physical function. Those with pre-obesity, versus normal weight, also had 3.7 [1.9-5.3] more years with limitation in physical function. The same pattern across BMI categories was observed for years of life with and without limitation in ADLs. In stratified analyses, similar associations of BMI with years of life with and without limitation in physical function and in ADLs were observed across gender, ethnicity, and educational status. CONCLUSIONS: The increasing global prevalence of obesity may result in an increase in years of life with limitation in physical function and in ADLs at older ages. Older adults, their families and healthcare systems should be cognizant of this issue.

Validation of the global activity limitation indicator in Taiwan.

BACKGROUND: The Global Activity Limitation Indicator (GALI) is a single-item measure of functional decline, it is widely used in Europe but it has never been validated in an Asian population. The aim of this study was to validate the GALI in a sample of older Taiwanese people and to explore whether it captured not only physical but also psychological limitations. METHODS: Data for 4961 individuals (mean age, 62.4 ± 9.4 years; 47.2% men) were obtained from a national representative refresh cohort of the 8th wave of the Taiwan Longitudinal Survey on Aging. Logistic regression analysis was used to examine associations among the GALI, activities of daily living (ADLs) and instrumental activities of daily living (IADLs) and to explore whether depressive symptoms (measured by the Center for Epidemiologic Studies Depression Scale, CES-D) could be an indicator of reporting limitations on the GALI. RESULTS: Responding to the GALI, 21.7% of the sample described themselves as 'limited.' In logistic regression, the GALI response was significantly associated with those who reported one or more ADL difficulties (odds ratio [OR] = 35.89, 95% confidence interval [CI] 21.10, 61.03) and IADL difficulties (OR = 13.37, 95%CI 10.09, 17.71), respectively. Furthermore, those with more depressive symptoms were more likely to report they were 'limited' on the GALI. CONCLUSIONS: These findings provided evidence that the GALI is a valid tool to assess general limitations in an Asian population. Furthermore, it captured psychological limitations to some extent. There were variations between Taiwan and European countries (as has been previously reported between European countries). The reporting level in the GALI by the Taiwan population was comparatively lower than that in European countries, highlighting the need to embrace cultural differences and to use caution when comparing GALI results across countries.

Disabled life expectancy with and without stroke: a 10-year Japanese prospective cohort study.

PURPOSE: A stroke is a debilitating condition that can cause lifelong disability, severely limiting the ability of individuals to perform daily activities. In Japan, strokes are the fourth leading cause of death; however, no previous studies have examined the influence of strokes on a disabled or disability-free life for older Japanese residents. This study aims to address this gap. METHODS: The study used data from the Nihon University Japanese Longitudinal Study of Aging (NUJLSOA) and incidence-based multistate life tables to estimate disabled and disability-free life expectancy based on the stroke status of Japanese residents aged 65 and older. RESULTS: Japanese stroke survivors aged 65 who experienced an initial disability-free state could expect to live approximately 3 fewer total years of life, 4-5 fewer years in a disability-free state, and 1-2 more years in a disabled state compared to those without history of a stroke (p < 0.05). For those disabled at the beginning of the survey interval, the differences between individuals with and without stroke history were also similar to those disability-free at the beginning of the survey interval (2-4 and 5-6 fewer total and disability-free years, respectively) (p < 0.05). The same pattern was observed for older age groups. CONCLUSION: Older adults who have experienced a stroke could experience a shorter total life expectancy, shorter disability-free life expectancy, and longer disabled life expectancy than those who have not experienced a stroke. These results can inform policymakers and rehabilitation practitioners on stroke survivor long-term care needs and their post-stroke health status.

Firing responses mediated via distinct nicotinic acetylcholine receptor subtypes in rat prepositus hypoglossi nuclei neurons.

We previously reported that cholinergic current responses mediated via nicotinic acetylcholine (ACh) receptors (nAChRs) in the prepositus hypoglossi nucleus (PHN), which participates in gaze control, can be classified into distinct types based on different kinetics and are mainly composed of α7- and/or non-α7-subtypes: fast (F)-, slow (S)-, and fast and slow (FS)-type currents. In this study, to clarify how each current type is related to neuronal activities, we investigated the relationship between the current types and the membrane properties and the firing responses that were induced by each current type. The proportion of the current types differed in neurons that exhibited different afterhyperpolarization (AHP) profiles and firing patterns, suggesting that PHN neurons show a preference for specific current types dependent on the membrane properties. In response to ACh, F-type neurons showed either one action potential (AP) or multiple APs with a short firing duration, and S-type neurons showed multiple APs with a long firing duration. The firing frequency of F-type neurons was significantly higher than that of S-type and FS-type neurons. An α7-subtype-specific antagonist abolished the firing responses of F-type neurons and reduced the responses of FS-type neurons but had little effect on the responses of S-type neurons, which were reduced by a non-α7-subtype-specific antagonist. These results suggest that the different properties of the current types and the distinct expression of the nAChR subtypes in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs. NEW & NOTEWORTHY Prepositus hypoglossi nucleus (PHN) neurons show distinct nicotinic acetylcholine receptor (nAChR)-mediated current responses. The proportion of the current types differed in the neurons that exhibited different afterhyperpolarization profiles and firing patterns. The nAChR-mediated currents with different kinetics induced firing responses of the neurons that were distinct in the firing frequency and duration. These results suggest that the different properties of the current types in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs.

Purinergic modulation of neuronal activity in the rat prepositus hypoglossi nucleus.

In the nervous system, adenosine 5'-trisphosphate (ATP) functions as a neurotransmitter and binds to ionotropic P2X receptors and metabotropic P2Y receptors. Although ATP receptors are expressed in the prepositus hypoglossi nucleus (PHN), which is a brainstem structure involved in controlling horizontal gaze, it is unclear whether ATP indeed affects the activity of PHN neurons. In this study, we investigated the effects of ATP on spontaneous firing of PHN neurons using whole-cell recordings in rat brainstem slices. Bath application of ATP increased or decreased the spontaneous firing rate of the neurons in a dose-dependent manner, indicating that ATP indeed affects PHN neuronal activity. To clarify the mechanisms of the ATP effects, we investigated the current responses of PHN neurons to a local application of ATP. The ATP application induced a fast inward (FI) current, a slow inward (SI) current, and/or a slow outward (SO) current in the neurons. The agonists of P2X and P2Y receptors induced FI and SI currents, respectively. The SO currents were not induced by the ATP agonists but were induced by adenosine, which may be extracellularly converted from ATP by ectonucleotidases. An antagonist of adenosine P1 (A1 ) receptors abolished the adenosine-induced SO currents and bath application of adenosine decreased the spontaneous firing rate of all PHN neurons tested. These results indicate that PHN neurons express functional purinoceptors and show that the FI, SI, and SO currents were mediated via P2X, P2Y, and A1 receptors, respectively.

Frailty and Associated Factors among Centenarians in the 5-COOP Countries.

BACKGROUND: The global number of centenarians is still strongly growing and information about the health and healthcare needs of this segment of the population is needed. This study aimed to estimate the prevalence of frailty among centenarians included in a multinational study and to investigate associated factors. METHODS: The 5-COOP study is a cross-sectional survey including 1,253 centenarians in 5 countries (Japan, France, Switzerland, Denmark, and Sweden). Data were collected using a standardized questionnaire during a face-to-face interview (73.3%), telephone interview (14.5%), or by postal questionnaire (12.2%). The 5 dimensions of the frailty phenotype (weight loss, fatigue, weakness, slow walking speed, and low level of physical activity) were assessed by using self-reported data. Factors associated with frailty criteria were investigated by using multivariate regression models. RESULTS: Almost 95% of the participants had at least 1 frailty criterion. The overall prevalence of frailty (3 criteria or more) was 64.7% (from 51.5% in Sweden to 77.6% in Switzerland), and 32.2% of the participants had 4 or 5 criteria. The most frequent criteria were weakness (84.2%), slow walking speed (77.6%), and low level of physical activity (72.5%), followed by fatigue (43.8%) and weight loss (23.8%). Factors associated with frailty included data collection modes, country of residence, gender, living in institution, depression, dementia, disability, falls, and sensory impairments. CONCLUSIONS: This study shows that reaching 100 years of age rarely goes without frailty and sheds light on factors associated with frailty at a very old age.