Association depressive symptoms with memory function and social capital before and during COVID-19 in community-dwelling older adults in rural Japan: A retrospective study with a longitudinal data.

OBJECTIVES: This study aimed to investigate the impact of memory function and social capital on depressive symptoms during the COVID-19 pandemic among older adults in rural Japan. METHODS: A retrospective study with longitudinal data was conducted during COVID-19 from May 2021 to November 2021 (T2) in Kurogawa, Japan. The candidate population for this study was 145 with the following requirements: (1) older individuals aged 65 years or above who were registered in the Kurogawa study, and (2) those with previous data (from November 2016 to February 2020; T1 as pre-pandemic). Memory function was assessed using the Wechsler Memory Scale-Revised Logical Memory II delayed recall part A (LM II-DR). Depressive symptoms were assessed using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15). Social capital was evaluated through civic participation, social cohesion, and reciprocity. Fear of the COVID-19 infection (FCV-19S) was evaluated. RESULTS: The final analysis included 96 participants (mean age = 81.0 years, SD = 4.8) Multivariate analysis for GDS-15 score by Mixed Model Repeated Measures (MMRM) revealed significant associations between LM II-DR (ß = -0.13, 95% CI: -0.21-0.05, p = 0.002) and FCV-19S during COVID-19 (ß = 0.08, 95% CI: 0.01-0.15, p = 0.02) with GDS-15 score. However, civic participation, social cohesion and reciprocity were not associated with GDS-15 score. CONCLUSIONS: Among older adults in rural Japan, memory function and fear of the COVID-19 infection were significantly associated with depressive symptoms in MMRM analysis. However, social capital was not associated with depressive symptoms. This highlights the need to address memory function and fear of the COVID-19 infection in interventions for older adults during crises like the COVID-19 pandemic.

Salivary 3-methoxy-4-hydroxyphenylglycol and MRI-based volume change of the precuneus in community-dwelling elderly people.

BACKGROUND: The noradrenergic systems in the brain maintain cognitive functions including attention/concentration and establishment of long-term memory. In addition, hypofunction of noradrenergic systems is supposed to be involved in the pathophysiology of Alzheimer's disease. In this study, we tried to examine the possible associations of concentrations of basal salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), a major metabolite of noradrenaline, and brain volume changes during 4 years in elderly people living in a rural community. METHODS: The survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 226 residents. Measurements of sMHPG and brain MRIs were collected at Time 1 (2005-2007). Follow-up brain MRIs were taken at Time 2 (2009-2011). A total of 70 participants (18 men, mean age 71.9 ± 4.8 years; 52 women, mean age 72.0 ± 4.3 years) completed this survey. Concentrations of sMHPG at baseline were divided into two groups using the mean value (12.83 ng/ml). We compared the brain volumes between groups with higher and lower sMHPG concentrations over time using voxel-based morphometry implemented with statistical parametric mapping. RESULTS: In participants with higher sMHPG concentrations at baseline, brain volumes including right precuneus were significantly larger 4 years after baseline than those with lower sMHPG concentrations at baseline. No interaction between sMHPG concentration and MRI acquisition interval was found. CONCLUSION: Our results suggest that higher sMHPG concentrations in elderly people might be associated with maintenance of brain volume, especially in brain regions closely related to cognitive function.

Development of an enzyme-linked immunosorbent assay for the quantification of O-Phosphoethanolamine in human plasma.

O-Phosphoethanolamine (PEA) is an endogenous substance that is attracting interest as a biomarker for depression, and thus there is a need to develop a simple analytical method that specifically measures PEA. Therefore, this study aimed to develop a simple and specific enzyme-linked immunosorbent assay (ELISA) for PEA. Anti-PEA antibody was obtained by immunizing mice with an antigen conjugated with mercaptosuccinyl bovine serum albumin using m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester (MBS). In this assay, the PEA to be quantified is chemically modified by benzoyl chloride that is allowed to compete with a PEA-MBS-HRP conjugate for binding to a limited amount of an anti-PEA antibody, which was used to coat the wells of a microtiter plate. This ELISA shows a linear range of detection of 0.11-27 µM, and a limit of quantification of 0.144 µM. The anti-PEA antibody showed high affinity for benzoyl PEA. No detectable cross-reactivity was found with benzoyl 2-aminoethanol, O-phospho-l-tyrosine or benzoyl sphingosine-1-phosphate. The values of plasma PEA levels measured by this ELISA were comparable to those measured by HPLC, and a strong correlation was observed between the values determined by the two methods. The developed ELISA should provide a valuable new tool for the quantification of PEA in human plasma.

Neuroinflammation in Late-Onset Schizophrenia: Viewing from the Standpoint of the Microglia Hypothesis.

Schizophrenia develops mainly in adolescence, but late-onset schizophrenia (LOS) is not uncommon. According to the international consensus, schizophrenia which develops over 40 years old is called LOS and psychosis which develops over 60 years old is called very late-onset schizophrenia-like psychosis (VLOS). Compared to early-onset schizophrenia (EOS) that develops before the age of 40 years, LOS and VLOS are reported to be more common in women, and there are clinically clear differences such as less involvement of genetic factors than EOS. This review outlines the abnormalities of the neuroimmune system in the pathophysiology of LOS, especially focusing on the role of microglia.

Association between cortisol and aging-related hippocampus volume changes in community-dwelling older adults: a 7-year follow-up study.

BACKGROUND: Identifying peripheral biomarkers related to modifiable risk factors to prevent dementia at an early stage will be extremely beneficial. We have been studying how older adults can maintain their mental health and continue to live in a familiar community. The aim of this study is to investigate the association between serum cortisol levels and brain volume among older adults in rural Japan. METHODS: This was a longitudinal study conducted in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and above, as reported previously. We conducted a survey twice. The first survey was conducted from October 2009 to March 2011 (Timepoint 1) and the second was conducted from November 2016 to September 2017 (Timepoint 2). Blood samples for serum cortisol levels analysis were collected from participants at Timepoint 1. Serum cortisol levels were measured using the enzyme-linked immunosorbent assay. The participants underwent brain MRI examinations, and Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) for cognitive function assessment at Timepoint 1 and Timepoint 2. We obtained 70 participants (16 men, mean age 72.69 ± 3.18 years; 54 women, mean age 72.69 ± 4.60 years, at Timepoint 1) for analysis. Correlation analysis was performed between serum cortisol levels at baseline (Timepoint 1) and brain volume (Timepoint 1, Timepoint 2, and Timepoint 1-Timepoint 2 difference) using voxel-based morphometry method. RESULTS: There was no significant difference in serum cortisol levels between men (72.32 ± 17.30 ng/ml) and women (76.60 ± 21.12 ng/ml) at baseline. Additionally, no effect of blood collection time on cortisol levels was observed in these participants. Small volume correction analysis at the cluster level by applying multiple comparison corrections (family-wise error; P < 0.05) showed a negative correlation between serum cortisol levels (Timepoint 1) and brain volume (Timepoint 2) within the region containing the left hippocampus. CONCLUSIONS: Serum cortisol levels may serve as a peripheral biomarker of age-related volume changes involving the hippocampus in older adults aged 65 years and above.

Association of orexin receptor antagonists with falls during hospitalization.

WHAT IS KNOWN AND OBJECTIVE: The use of hypnotics, especially benzodiazepines (BZs), increases the risk of falls. Regarding the association of orexin receptor antagonists with fall risk, consistent results have not been obtained for suvorexant, and studies of lemborexant have not been reported. Therefore, this study investigated whether orexin receptor antagonists, including lemborexant, increase the risk of falls. METHODS: Data were obtained from the medical records of patients hospitalized at Saga University Hospital in Japan between July 2020 and April 2021. Patients were retrospectively divided into the fall and non-fall groups, and the groups were compared for medication usage. RESULTS AND DISCUSSION: The fall and non-fall groups included 132 and 6857 patients respectively. A significantly higher proportion of patients in the fall group used hypnotics (40.2% vs. 21.7%; p < 0.0001). Hypnotics remained significantly associated with a higher risk of falls after adjusting for confounders (adjusted odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.13-2.48, p = 0.01). In particular, the use of benzodiazepines was associated with a significantly higher risk of falls (adjusted OR = 2.08, 95% CI = 1.38-3.15, p = 0.0005). Meanwhile, suvorexant use was not linked to the risk of falls, and lemborexant use was associated with a significantly lower risk of falls (adjusted OR = 0.27, 95% CI = 0.09-0.84, p = 0.02). WHAT IS NEW AND CONCLUSION: The use of hypnotics is a risk factor for falls, but orexin receptor antagonists may represent a safe option for patients requiring hypnotics. Our results provide evidence supporting the safety of these drugs.

ProBDNF induces sustained elevation of intracellular Ca2+ possibly mediated by TRPM7 channels in rodent microglial cells.

Microglia are intrinsic immune cells that release factors including pro- and anti-inflammatory cytokines, nitric oxide (NO) and neurotrophins following activation in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+ ]i) is important for microglial functions, such as the release of cytokines or NO from activated microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia. Interestingly, proBDNF, the precursor form of mature BDNF, and mature BDNF elicit opposing neuronal responses in the brain. Mature BDNF induces sustained intracellular Ca2+ elevation through the upregulation of the surface expression of TRPC3 channels in rodent microglial cells. In addition, TRPC3 channels are important for the BDNF-induced suppression of NO production in activated microglia. In this study, we observed that proBDNF and mature BDNF have opposite effects on the relative expression of surface p75 neurotrophin receptor (p75NTR ) in rodent microglial cells. ProBDNF induces a sustained elevation of [Ca2+ ]i through binding to the p75NTR , which is possibly mediated by Rac 1 activation and TRPM7 channels in rodent microglial cells. Flow cytometry showed that proBDNF increased the relative surface expression of TRPM7. Although proBDNF did not affect either mRNA expression of pro- and anti-inflammatory cytokines or the phagocytic activity, proBDNF potentiates the generation of NO induced by IFN-γ and TRPM7 channels could be involved in the proBDNF-induced potentiation of IFN-γ-mediated production of NO. We show direct evidence that rodent microglial cells are able to respond to proBDNF, which might be important for the regulation of inflammatory responses in the brain.

Serum Oxytocin Levels and Logical Memory in Older People in Rural Japan.

OBJECTIVE: The present study aimed to investigate the relationship between serum oxytocin (OT) and logical memory among older people in rural Japan. METHODS: This was a cross-sectional study using a survey conducted from October 2009 through March 2011. Most of the study was conducted as part of a national prevalence survey of dementia in Japan. The final sample comprised 385 community-dwelling people aged 65 years or older living in rural Japan. The mean age and standard deviation were 75.7 ± 6.76 years (144 men, mean age 75.0 ± 6.48 years; 241 women, mean age 76.2 ± 6.91 years). The participants underwent screening examinations for a prevalence survey of dementia. The screening examinations were the Mini-Mental State Examination, Clinical Dementia Rating, and "logical memory A" from the Wechsler Memory Scale-Revised (WMSR). We used the WMSR Logical Memory II delayed recall score (LM II-DR) to assess logical memory. Levels of serum OT were obtained using the enzyme immunoassay method. RESULTS: Serum OT levels were significantly higher among women than men. The present study revealed that serum OT levels were positively associated with LM II-DR in older women living in rural Japan in multiple linear regression analyses. CONCLUSIONS: The present results suggested a positive correlation between OT and logical memory in older women living in rural Japan.

No association of both serum pro-brain-derived neurotrophic factor (proBDNF) and BDNF concentrations with depressive state in community-dwelling elderly people.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is involved in emotional and cognitive function. Low-BDNF levels occur in patients with depression, while proBDNF, a precursor of BDNF with the opposite physiological function, increases in major depression. However, it is unclear whether BDNF and proBDNF are associated with depression in the elderly. The present study aimed to investigate whether serum proBDNF and BDNF are associated with depressive state in community-dwelling elderly people. METHODS: This was a cross-sectional study conducted in Kurogawa-cho Imari, Saga Prefecture, Japan, in people aged ≥65 years. Depressive state was assessed using the Geriatric Depression Scale-Short Form (Japanese version) (GDS). Of the 274 patients who undertook the GDS, those with a medical history affecting cognitive function were excluded, as were those with Mini-Mental State Examination score ≥ 24 or a Clinical Dementia Rating < 0.5. Further, we used delayed recall of 'logical memory A' from the Wechsler Memory Scale-Revised (LMII-DR) for memory assessment. RESULTS: The final sample consisted of 155 individuals (mean age 75.4 ± 6.8 years; 55 men, mean age 74.8 ± 5.9 years; 100 women, mean age 76.3 ± 7.1 years). In the GDS, 139 participants showed a normal score (0-4) and 16 showed depressive tendencies or depression (score: ≥ 5). After examining confounders of the GDS, logistic regression using categorical covariates showed a negative significant difference between depressive state and serum BDNF in the low-BDNF group only, with a positive correlation in the trend test. None of the analyses showed any association between GDS and proBDNF levels. CONCLUSION: ProBDNF and BDNF levels seemed not to be associated with depressive state in community-dwelling elderly people.

ATP and repetitive electric stimulation increases leukemia inhibitory factor expression in astrocytes: A potential role for astrocytes in the action mechanism of electroconvulsive therapy.

AIM: Electroconvulsive therapy (ECT) is effective for psychiatric disorders. However, its action mechanism remains unclear. We previously reported that transcription factor 7 (TCF7) was increased in patients successfully treated with ECT. TCF7 regulates Wnt pathway, which regulates adult hippocampal neurogenesis. Adult hippocampal neurogenesis is involved in the pathophysiology of psychiatric disorders. Astrocytes play a role in adult hippocampal neurogenesis via neurogenic factors. Of astrocyte-derived neurogenic factors, leukemia inhibitory factor (LIF) and fibroblast growth factor 2 (FGF2) activate Wnt pathway. In addition, adenosine triphosphate (ATP), released from excited neurons, activates astrocytes. Therefore, we hypothesized that ECT might increase LIF and/or FGF2 in astrocytes. To test this, we investigated the effects of ATP and electric stimulation (ES) on LIF and FGF2 expressions in astrocytes. METHODS: Astrocytes were derived from neonatal mouse forebrain and administered ATP and ES. The mRNA expression was estimated with quantitative reverse-transcription polymerase chain reaction. Protein concentration was measured with ELISA. RESULTS: ATP increased LIF, but not FGF2, expression. Multiple ES, but not single, increased LIF expression. Knockdown of P2X2 receptor (P2X2R) attenuated ATP-induced increase of LIF mRNA expression. In contrast, P2X3 and P2X4 receptors intensified it. CONCLUSION: P2X2R may mediate ATP-induced LIF expression in astrocytes and multiple ES directly increases LIF expression in astrocytes. Therefore, both ATP/P2X2R and multiple ES-induced increases of LIF expression in astrocytes might mediate the efficacy of ECT on psychiatric disorders. Elucidating detailed mechanisms of ATP/P2X2R and multiple ES-induced LIF expression is expected to result in the identification of new therapeutic targets for psychiatric disorders.

Low-Grade Inflammation Is Associated with Apathy Indirectly via Deep White Matter Lesions in Community-Dwelling Older Adults: The Sefuri Study.

Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white matter lesions (DWMLs). Path analysis based on structural equation modeling (SEM) indicated that the direct path from the log10 hsCRP to the DWMLs was significant (ß = 0.119, p = 0.039). The direct paths from the metabolic syndrome to the log10 hsCRP and to the DWMLs were also significant. The direct path from the DWMLs to apathy (ß = -0.165, p = 0.007) was significant, but the direct path from the log10 hsCRP to apathy was not significant. Inflammation (i.e., elevated serum hsCRP levels) was associated with DWMLs independent of common vascular risk factors, while DWMLs were associated with apathy. The present analysis with SEM revealed the more realistic scheme that low-grade inflammation was associated with apathy indirectly via DWMLs in community-dwelling older adults.

Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia.

BACKGROUND: Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer's disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells. METHODS: We examined whether pretreatment with donepezil affects the intracellular Ca2+ mobilization using fura-2 imaging and tested the effects of donepezil on phagocytic activity by phagocytosis assay in rodent microglial cells. RESULTS: In this study, we observed that pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation in both rat HAPI and mouse primary microglial cells. On the other hand, pretreatment with donepezil did not suppress the mRNA expression of both TNFR1 and TNFR2 in rodent microglia we used. Pretreatment with acetylcholine but not donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the nicotinic α7 receptors. In addition, sigma 1 receptors were not involved in the donepezil-induced suppression of the TNFα-mediated intracellular Ca2+ elevation. Pretreatment with donepezil suppressed the TNFα-induced intracellular Ca2+ elevation through the PI3K pathway in rodent microglial cells. Using DAF-2 imaging, we also found that pretreatment with donepezil suppressed the production of NO induced by TNFα treatment and the PI3K pathway could be important for the donepezil-induced suppression of NO production in rodent microglial cells. Finally, phagocytosis assay showed that pretreatment with donepezil promoted phagocytic activity of rodent microglial cells through the PI3K but not MAPK/ERK pathway. CONCLUSIONS: These suggest that donepezil could directly modulate the microglial function through the PI3K pathway in the rodent brain, which might be important to understand the effect of donepezil in the brain.

An association between belief in life after death and serum oxytocin in older people in rural Japan.

OBJECTIVE: Previous research suggests that spirituality/religiosity has benefits for both mental and physical health, measured using biological indices such as cortisol and IL-6. However, there have been few studies concerning the association of religious beliefs with oxytocin, a neuropeptide hormone secreted by the pituitary. Levels of peripheral oxytocin are thought to reflect the strength of bonding and stress regulation in social relationships. As such, the oxytocin system may underpin the biological mechanisms by which belief in life after death is associated with good mental and physical health. Here, we examine associations between oxytocin and belief in life after death. METHODS: We recruited 317 community-dwelling people, aged 65 or older, without cognitive or mental deficits, and living in rural Japan. We recorded demographics, belief in life after death, and logical memory using the Wechsler Memory Scale. Levels of serum oxytocin were obtained using an enzyme immunoassay method. RESULTS: Serum oxytocin levels were higher among women than men and were negatively associated with strength of belief in life after death. CONCLUSIONS: Our findings could be interpreted differently depending on whether the anxiogenic or anxiolytic function of the oxytocin system is considered. Greater endorsement of afterlife beliefs may reduce secure attachment. Alternatively, based on the literature suggesting that basal levels of oxytocin are lower in those with reduced relational distress or anxiety, afterlife beliefs may play a role in these reductions. Copyright © 2016 John Wiley & Sons, Ltd.

TRPC Channels and Brain Inflammation.

Nonresolving low-grade inflammation is supposed to underly the basis of chronic disorders including cardiovascular diseases, cancer, diabetes, obesity, and psychiatric disorders such as depression and Alzheimer's diseases. There is increasing evidence suggesting that pathophysiology of psychiatric disorders is related to the inflammatory responses mediated by microglial cells. Elevation of intracellular Ca2+ is important for the activation of microglial cell functions, including proliferation, release of NO, cytokines, and BDNF. It has been shown that alteration of intracellular Ca2+ signaling underlies the pathophysiology of psychiatric disorders, including depression. BDNF induces a sustained intracellular Ca2+ elevation through the upregulation of the surface expression of TRPC3 channels in rodent microglial cells. Microglial cells are able to respond to BDNF, which may be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of psychiatric disorders. We also need to study the effect of proBDNF on microglial cells especially by focusing on the TRPC channels.

Aripiprazole-Associated Hypoprolactinemia in the Clinical Setting.

BACKGROUND: The increase in prolactin (PRL) levels is a common adverse effect that occurs when using conventional and atypical antipsychotic drugs. Aripiprazole (ARI) is beneficial for antipsychotic-associated hyperprolactinemia but has been reported to decrease PRL secretion. Therefore, we investigated blood levels of PRL in patients who had taken ARI alone or in combination with other antipsychotics. METHODS: Retrospective information was obtained from 25 psychiatric patients who were prescribed ARI, and the blood levels of PRL were measured. RESULTS: The incidence of hypoprolactinemia in the current study was 44.0% (11/25). Eighteen patients were treated with ARI alone and 7 received ARI in combination with other antipsychotics. The PRL value of patients who took ARI alone was significantly lower than those who were also taking other antipsychotics (5.45 ± 3.93 vs 10.85 ± 5.53, P = 0.02; mean ± SD). There was no significant correlation of the PRL levels and dose of ARI used in the 18 patients who had taken ARI alone. LIMITATIONS: This was a retrospective study, and the data were obtained from a small number of psychiatric patients treated with ARI. CONCLUSIONS: Monitoring of PRL levels in patients treated with ARI may be useful in minimizing hypoprolactinemia, which has the potential to negatively impact patients. In particular, hypoprolactinemia as a consequence of taking ARI should be discussed with patients of childbearing age and those with immune deficiencies.

A patient with Alzheimer's disease complicated by elderly-onset Cushing's syndrome who had undergone surgical treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia.

Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the median age of presentation of CS and that of Alzheimer's disease. We herein report a case of a patient with Alzheimer's disease complicated by elderly-onset CS who had undergone surgical treatment for adrenal hyperplasia. Surgical correction of hypercortisolism seems to have slowed the progression of brain volume loss and cognitive dysfunction and improved psychiatric symptoms such as visual hallucination, restlessness, and psychomotor excitement. These improvements have remarkably reduced the burden on the patient's caregivers. The present case suggests that subclinical CS may be present, particularly in rapidly progressive dementia, and that surgical treatment of CS for neuropsychiatric symptoms is useful.

Abnormal behaviours during pramipexole treatment for Cotard's syndrome: a case report.

Cotard's syndrome is a relatively rare condition that involves a delusion of negation in which an individual believes he or she has lost his or her soul, is dead, or is without functional body systems. This syndrome is observed in various neuropsychiatric disorders but most commonly in mood disorders. Pramipexole has often been used in the adjunctive treatment of both bipolar and unipolar depression, and it is known to cause rare but serious adverse effects such as compulsive behaviours in the treatment of Parkinson's disease. Here we report a case of Cotard's syndrome in treatment-resistant major depression associated with abnormal behaviours that might be caused by pramipexole. In the present case, the patient's abnormal behaviours gradually disappeared about 2 months after the discontinuation of pramipexole. The hypoperfusion in the bilateral parieto-occipital lobe found on single-photon emission computed tomography suggests the presence of Lewy body disease pathology. Nonetheless, the patient's abnormal behaviours disappeared after the discontinuation of pramipexole, indicating that they are mainly attributable to pramipexole treatment. However, the possible existence of Lewy body pathology could facilitate the emergence of abnormal behaviours after treatment with pramipexole. The patient's abnormal behaviours, such as eating other patients' food and taking her medicine before the scheduled time, might differ from typical compulsive behaviours induced by pramipexole (such as pathological gambling and hypersexuality), but they could be regarded as disinhibition. Therefore, we should follow up on the clinical course of this case carefully through neuroimaging investigation and neurocognitive assessment.

Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia.

Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.

Belief in life after death, salivary 3-methoxy-4-hydroxyphenylglycol, and well-being among older people without cognitive impairment dwelling in rural Japan.

OBJECTIVES: Research has found that spirituality/religiosity has a salutary association with mental/physical health. However, the association of belief in life after death with well-being has rarely been studied, and the same is true of its association with biological indices, such as monoamine transmitters. Therefore, we examined the associations between well-being and religiosity, salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), and demographic characteristics. METHODS: The participants were 346 community-dwelling people, aged 65 years or older, without cognitive or mental deficits, in rural Japan. Measures of religiosity consisted of belief in life after death, attachment to life, and experiences related to death and religion. The measures were assessed by scales specifically suited for Japanese religious orientations. Participants' well-being was assessed by a life satisfaction scale containing two subscales. We also measured sMHPG, a major metabolite of noradrenaline that is thought to reflect certain psychological states, such as psychomotor retardation and effortful attention. RESULTS: One subscale of life satisfaction was positively associated with belief in life after death and sMHPG, and the other life satisfaction subscale was positively associated with education and death/religion-related experiences (e.g., visiting family graves or loss of a friend). Gender differences were found in afterlife beliefs and each life satisfaction subscale. CONCLUSIONS: These results suggest that religiosity, including belief in life after death and death/religion-related experiences, is salubriously associated with mental health among older people, especially women, living in rural Japan. The basal level of sMHPG was positively associated with life satisfaction, but not with belief in life after death.