[Relationship between work engagement and organizational justice among hospital nurses].

Objective　This study aimed to clarify the relationship between organizational justice and work engagement among nurses.Methods　Japanese nurses working in a medium-sized hospital in the Tokyo metropolitan area were surveyed using a self-administered questionnaire. We conducted a stepwise multiple regression analysis with scores from the Japanese version of the Utrecht Work Engagement Scale (UWES-J) as the dependent variable and scores from the Japanese version of the Organizational Justice Scale (OJS-J), age, sex, position, employment status, shift work, self-efficacy, social support, work control, and work quantitative load as the independent variables. Additionally, a stepwise multiple regression analysis was conducted for each OJS-J subscale score.Results　The questionnaire was distributed to 270 nurses, of whom 219 (83.0% response rate) provided valid responses. With the UWES-J as the dependent variable, Model 1 adjusted only for age and sex; Model 2 adjusted for position, employment status, shift work, and self-efficacy score; and Model 3 adjusted for the social support, work control, and work quantitative load scores. Model 2 and Model 3 showed a significant association to the positive direction between UWES-J and OJS-J (Model 3: ß=0.202, P<0.01, R2=0.363). Furthermore, when the same analysis was conducted for each OJS-J subscale score, a significant association was found between procedural justice scores and the UWES-J (Model 3: ß=0.165, P<0.05, R2=0.383). Neither model found a significant difference between distributional equity scores and information equity scores.Conclusion　The results of this study examining the relationship between work engagement and organizational justice among hospital nurses showed that work engagement was associated with organizational justice, especially procedural justice. These results suggest that maintaining and improving organizational justice is important for improving nurses' work engagement.

Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery.

OBJECTIVE: This study aimed to compare the quality of life (QoL) and psychological issues of patients with papillary thyroid microcarcinoma (PMC) who were under active surveillance (AS) and those who underwent immediate surgery (OP). METHODS: This was a cross-sectional study conducted on 347 patients with low-risk PMC who were under AS (n = 298) or who underwent OP (n = 49). They were asked to complete two questionnaires (thyroid cancer-specific health-related QoL [THYCA-QoL] and the Hospital Anxiety and Depression Scale [HADS]). The results between the AS and OP groups were compared. RESULTS: The mean ages of patients in the AS and OP groups were 58.6±12.5 and 58.4±13.1 years (P =.94), respectively, and the male ratios were 34/298 (11%) and 2/49 (4.1%) (P =.14), respectively. The median follow-up periods from diagnosis in the AS and OP groups were 56.5 months (interquartile range [IQR], 32 to 88 months) and 84 months (IQR, 64 to 130 months) (P<.001), respectively. In the THYCA-QoL questionnaire, the OP group had more complaints about "voice" (P<.001), "psychological" (P =.025), "problems with scar" (P<.001), and "gained weight" (P =.047) than the AS group. Other scales of the THYCA-QoL were comparable in the two groups. In the HADS questionnaire, the AS group had significantly better anxiety (P =.020), depression (P =.027), and total scores (P =.014) than the OP group. CONCLUSION: PMC patients in the OP group had more complaints and were more anxious and depressed than the AS group. These findings suggest that AS is a reasonable alternative to surgery for patients with low-risk PMC from the point of view of QoL and psychology. ABBREVIATIONS: AS = active surveillance; CI = confidence interval; HADS = Hospital Anxiety and Depression Scale; LT4 = levothyroxine; OP = immediate surgery; PMC = papillary microcarcinoma; PTC = papillary thyroid carcinoma; QoL = quality of life; STAI = State-Trait Anxiety Inventory; THYCA-QoL = thyroid cancer-specific health-related quality of life; TSH = thyrotropin.

Neural substrate of a cognitive intervention program using Go game: a positron emission tomography study.

BACKGROUND: Influence of cognitive intervention programs on brain activity has not been enough explored. AIMS: The aims of the present study were to clarify changes in brain activity from a cognitive intervention program utilizing the board game "Go" and to examine the relationship between brain activity and the acquisition of Go skills. METHODS: Eighteen community-dwelling older adults were randomly assigned either to an intervention group (IG), in which members attended 12 Go lessons either in groups or individually using tablet computers, or a control group (CG), in which members attended health education lectures unrelated to Go. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), cognitive assessments, and Go tests were performed before and after the intervention. RESULTS: The results showed different patterns of regional FDG uptake in both groups: regional cerebral glucose metabolism was significantly increased in the left middle temporal gyrus (MTG) and bilateral putamen (p < 0.01; cluster level) in the IG, and in the left superior frontal gyrus in the CG, (p < 0.01; cluster level). Furthermore, Go test scores were significantly improved in the IG (p < 0.05), and a significant association was observed between changes in Go test scores and glucose metabolism in the left MTG (p < 0.05). CONCLUSIONS AND DISCUSSION: This study indicates that a cognitive intervention program using Go may enhance brain activity. Further studies with larger populations and longer observation periods are needed to clarify the neural mechanisms underlying our Go intervention program.

Effects of Brief Cognitive Behavioral Therapy for Insomnia on Improving Depression Among Community-Dwelling Older Adults: A Randomized Controlled Comparative Study.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve depressive symptoms in older adults with comorbid insomnia and depression. However, it remains unclear whether brief CBT-I is effective for improving depressive symptoms in community-dwelling older adults with insomnia symptoms of varying severity. AIM: This study sought to examine the effectiveness of a brief CBT-I intervention delivered by public health nurses to improve depressive symptoms among older adults recruited from a community setting. METHODS: This randomized controlled study compared sleep status and depression at baseline and a 3-month follow-up using a wait-list control design. Depression was evaluated using the Geriatric Depression Scale short form (GDS-SF). RESULTS: The GDS-SF scores in the CBT-I group improved over time (p < .01), with an effect size (Cohen's d) of 0.34 (95% CI [0.16, 0.58]). The results demonstrated the effectiveness of a brief CBT-I intervention for depression, although the effect size was small. LINKING EVIDENCE TO ACTION: A brief CBT-I intervention consisting of sleep hygiene education, stimulus control, sleep restriction, cognitive restructuring, and relaxation is effective for improving depressive symptoms among older adults in the community.

[Effects of Brief Cognitive Behavioral Therapy for insomnia on sleep and usage of hypnotics among community-dwelling older adults: Randomized controlled trial].

Objectives　Chronic insomnia is common in late adulthood. A non-pharmacological approach should take priority in the treatment of insomnia for the elderly. Many studies have shown the efficacy of Cognitive Behavioral Therapy for Insomnia (CBT-I) for elderly diagnosed with insomnia. However the effect of CBT-I on mild insomnia among older adults in community settings has not been ascertained. We conducted a randomized controlled trial to evaluate the effectiveness of a brief CBT-I delivered by nurses, which is feasible in community settings, to improve sleep quality and decrease the dose of hypnotics use for older adults.Methods　Participants aged 60 years and over were enrolled in this study. The participants in the intervention group were administrated the brief CBT-I consisting of a group session (60 min) and an individual session (30 min). The primary outcomes were the score differences in the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI). The secondary outcomes were the change in the proportion of people diagnosed with insomnia and the dose of hypnotics used. The follow-up period was 3 months.Results　The score on PSQI in the intervention group (n=41) significantly decreased compared to the control group (n=38). The effect size (Cohen's d) was 0.56 (95% Confidence interval [CI], 0.07 to 1.05). The score on ISI also decreased significantly and Cohen's d was 0.77 (95%CI, 0.27 to 1.26). According to subgroup analysis, Number Needed to Treat (NNT) for improvement of insomnia was 2.8 (95%CI, 1.5-17.2) and NNT for decreasing of dose of hypnotics use was 2.8 (95%CI, 1.5-45.1).Conclusion　The present results have demonstrated that the brief CBT-I significantly improved subjective evaluation of sleep quality and insomnia symptoms among the elderly. In addition, the brief CBT-I decreased the usage of hypnotics. Further studies are needed in terms of the procedure and the effects of brief CBT-I for older adults living in a community.

Rearing-environment-dependent hippocampal local field potential differences in wild-type and inositol trisphosphate receptor type 2 knockout mice.

KEY POINTS: Mice reared in an enriched environment are demonstrated to have larger hippocampal gamma oscillations than those reared in isolation, thereby confirming previous observations in rats. To test whether astrocytic Ca2+ surges are involved in this experience-dependent LFP pattern modulation, we used inositol trisphosphate receptor type 2 (IP3 R2)-knockout (KO) mice, in which IP3 /Ca2+ signalling in astrocytes is largely diminished. We found that this experience-dependent gamma power alteration persists in the KO mice. Interestingly, hippocampal ripple events, the synchronized events critical for memory consolidation, are reduced in magnitude and frequency by both isolated rearing and IP3 R2 deficiency. ABSTRACT: Rearing in an enriched environment (ENR) is known to enhance cognitive and memory abilities in rodents, whereas social isolation (ISO) induces depression-like behaviour. The hippocampus has been documented to undergo morphological and functional changes depending on these rearing environments. For example, rearing condition during juvenility alters CA1 stratum radiatum gamma oscillation power in rats. In the present study, hippocampal CA1 local field potentials (LFP) were recorded from bilateral CA1 in urethane-anaesthetized mice that were reared in either an ENR or ISO condition. Similar to previous findings in rats, gamma oscillation power during theta states was higher in the ENR group. Ripple events that occur during non-theta periods in the CA1 stratum pyramidale also had longer intervals in ISO mice. Because astrocytic Ca2+ elevations play a key role in synaptic plasticity, we next tested whether these changes in LFP are also expressed in inositol trisphosphate receptor type 2 (IP3 R2)-knockout (KO) mice, in which astrocytic Ca2+ elevations are largely diminished. We found that the gamma power was also higher in IP3 R2-KO-ENR mice compared to IP3 R2-KO-ISO mice, suggesting that the rearing-environment-dependent gamma power alteration does not necessarily require the astrocytic IP3 /Ca2+ pathway. By contrast, ripple events showed genotype-dependent changes, as well as rearing condition-dependent changes: ISO housing and IP3 R2 deficiency both lead to longer inter-ripple intervals. Moreover, we found that ripple magnitude in the right CA1 tended to be smaller in IP3 R2-KO. Because IP3 R2-KO mice have been reported to have depression phenotypes, our results suggest that ripple events and the mood of animals may be broadly correlated.

Comparison of Absorbents and Drugs for Internal Decorporation of Radiocesium: Advances of Polyvinyl Alcohol Hydrogel Microsphere Preparations Containing Magnetite and Prussian Blue.

Radiocesium nuclides, used as a gamma ray source in various types of industrial equipments and found in nuclear waste, are strictly controlled to avoid their leakage into the environment. When large amounts of radiocesium are accidentally incorporated into the human body, decorporation therapy should be considered. Although standard decorporation methods have been studied since the 1960s and were established in the 1970s with the drug Radiogardase(®) (a Prussian blue preparation), application of recent advances in pharmacokinetics and ethical standards could improve these methods. Here we designed a modern dosage form of hydrogel containing cesium-absorbents to alleviate intestinal mucosa irritation due to the cesium-binding capacity of the absorbents. The effectiveness of the dosage form on fecal excretion was confirmed by quantitative mouse experiments. The total cesium excretion rate of the crystal form (1.37±0.09) was improved by the hydrogel form (1.52±0.10) at the same dose of Prussian blue, with a longer gastrointestinal tract transit time. Using a mouse model, we compared the effects of several drugs on fecal and urinary excretion of internal cesium, without the use of absorbents. Only phenylephrine hydrochloride significantly enhanced cesium excretion (excretion rate of 1.17±0.08) via the urinary pathway, whereas none of the diuretic drugs tested had this effect. These findings indicate that modifying the dosage form of cesium absorbents is important for the decorporation of internal radiocesium contamination.

Reduced axonal localization of a Caps2 splice variant impairs axonal release of BDNF and causes autistic-like behavior in mice.

Ca(2)(+)-dependent activator protein for secretion 2 (CAPS2 or CADPS2) potently promotes the release of brain-derived neurotrophic factor (BDNF). A rare splicing form of CAPS2 with deletion of exon3 (dex3) was identified to be overrepresented in some patients with autism. Here, we generated Caps2-dex3 mice and verified a severe impairment in axonal Caps2-dex3 localization, contributing to a reduction in BDNF release from axons. In addition, circuit connectivity, measured by spine and interneuron density, was diminished globally. The collective effect of reduced axonal BDNF release during development was a striking and selective repertoire of deficits in social- and anxiety-related behaviors. Together, these findings represent a unique mouse model of a molecular mechanism linking BDNF-mediated coordination of brain development to autism-related behaviors and patient genotype.

CAPS1 deficiency perturbs dense-core vesicle trafficking and Golgi structure and reduces presynaptic release probability in the mouse brain.

Ca(2+)-dependent activator protein for secretion 1 (CAPS1) plays a regulatory role in the dense-core vesicle (DCV) exocytosis pathway, but its functions at the cellular and synaptic levels in the brain are essentially unknown because of neonatal death soon after birth in Caps1 knock-out mice. To clarify the functions of the protein in the brain, we generated two conditional knock-out (cKO) mouse lines: 1) one lacking Caps1 in the forebrain; and 2) the other lacking Caps1 in the cerebellum. Both cKO mouse lines were born normally and grew to adulthood, although they showed subcellular and synaptic abnormalities. Forebrain-specific Caps1 cKO mice showed reduced immunoreactivity for the DCV marker secretogranin II (SgII) and the trans-Golgi network (TGN) marker syntaxin 6, a reduced number of presynaptic DCVs, and dilated trans-Golgi cisternae in the CA3 region. Cerebellum-specific Caps1 cKO mice had decreased immunoreactivity for SgII and brain-derived neurotrophic factor (BDNF) along the climbing fibers. At climbing fiber-Purkinje cell synapses, the number of DCVs was markedly lower and the number of synaptic vesicles was also reduced. Correspondingly, the mean amplitude of EPSCs was decreased, whereas paired-pulse depression was significantly increased. Our results suggest that loss of CAPS1 disrupts the TGN-DCV pathway, which possibly impairs synaptic transmission by reducing the presynaptic release probability.

Association between social group participation and perceived health among elderly inhabitants of a previously methylmercury-polluted area.

OBJECTIVE: This study attempted to clarify the association between participation in a social group and perceived health among elderly residents of a previously methylmercury-polluted area in Japan. METHODS: We conducted a cross-sectional study using eligible subjects from the Shiranui Sea coastal area, where mercury poisoning due to daily intake of fish and shellfish had previously caused some residents to develop the neurological disorder "Minamata disease (MD)." In the present study, we selected subjects aged ≥65 years who had never been diagnosed with MD or applied for medical treatment compensation. RESULTS: A logistic regression model after adjusting for confounding factors showed that membership in a hobby or volunteer group was associated with good perceived health (odds ratio 1.97, 95 % confidence interval 1.02-3.80). CONCLUSION: Our results showed that the effects of membership in social groups on perceived health were not equal across all social groups, with only hobby- or volunteer-related groups having a positive effect on perceived health. Our findings suggested that promoting participation in a social group such as hobby- or volunteer-related groups can help improve perceived health among elderly individuals who had experienced environmental pollution incidents.

Perspectives of Japanese elders and their healthcare providers on use of wearable technology to monitor their health at home: A qualitative exploration.

BACKGROUND: With 24 million Japanese elderly aging at home, the challenges of managing chronic conditions are significant. As many Japanese elders manage multiple chronic conditions, investigating the usefulness of wearable health devices for this population is warranted. AIM: The purpose of this qualitative study, using grounded theory, was to explore the perspectives of Japanese elders, their caretakers, and their healthcare providers on the use of technology and wearable devices to monitor health conditions and keep Japanese elders safe at home. METHODS: In conducting this study, a community advisory board was first established to guide the research design; six focus groups and two one-on-one interviews were conducted, with a total of 21 participants. RESULTS: Four major themes emerged from the analysis: 1) Current Status of Health Issues Experienced by Japanese Elders and Ways of Being Monitored; 2) Current Use of Monitoring Technology and Curiosity about Use of the Latest Digital Technology to Keep Elderly Healthy at Home; 3) Perceived Advantages of Wearing Sensor Technology; and 4) Perceived Disadvantages of Wearing Technology. Many of the elderly participants were interested in using monitoring devices at home, particularly if not complicated. Healthcare workers found monitoring technologies particularly useful during the isolation of the COVID-19 pandemic. Elderly participants felt cost and technical issues could be barriers to using monitoring devices. CONCLUSION: While there are challenges to utilizing monitoring devices, the potential to aid the aging population of Japan justifies further investigation into the effectiveness of these devices. This study was not registered with a research trial registry.

MR diagnosis of SCC arising within ovarian cystic teratomas: analysis of mural nodule characteristics.

PURPOSE: This study aims to evaluate and identify magnetic resonance (MR) findings of mural nodules to detect squamous cell carcinoma arising from ovarian mature cystic teratoma (SCC-MCT). METHODS: This retrospective study examined 135 patients (SCC-MCTs, n = 12; and benign MCTs, n = 123) with confirmed diagnoses across five different institutions between January 2010 and June 2022. Preoperative MR images for each patient were independently assessed by two experienced radiologists and analyzed following previously reported findings (PRFs): age, tumor size, presence of mural nodules, size of mural nodule, and the angle between mural nodule and cyst wall (acute or obtuse). Furthermore, this study evaluated four mural nodule features-diffusion restriction, fat intensity, Palm tree appearance, and calcification-and the presence of transmural extension. RESULTS: There were significant differences between the SCC-MCT and benign MCT groups in terms of all PRFs and all mural nodule findings (p < 0.01). Among the PRFs, "tumor size" demonstrated the highest diagnostic performance, with a sensitivity of 83.3% and a specificity of 88.6%. A combination of the aforementioned four mural nodule findings showed a sensitivity and specificity of 83.3% and 97.6%, respectively, for the diagnosis of SCC-MCT. Regarding diagnosis based on a combination of four mural nodule findings, the specificity was significantly higher than the diagnosis based on tumor size (p = 0.021). Based on these mural nodule findings, three SCC-MCT patients without transmural invasion could be diagnosed. CONCLUSION: Mural nodule MR findings had a higher diagnostic performance than PRFs for SCC-MCT and can potentially allow early detection of SCC-MCTs.

Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment.

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer's disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

Association between early methylmercury exposure and functional health among residents of the Shiranui Sea communities in Japan.

The objective of this study was to evaluate the effect of estimated historical methylmercury exposure on the functional health of residents living in the Shiranui Sea communities in Japan. Functional health was measured by self-reported activities of daily living (ADL). Study areas were categorized into high, medium and low methylmercury exposure areas according to their location or distance from the Shiranui Sea. We estimated the adjusted prevalence odds ratios of impaired ADL in relation to exposure using a logistic regression model. Compared with residents in the low-exposure area, residents in the high-exposure area were significantly associated with a higher prevalence odds ratio (OR) for impaired ADL after adjustment for confounding factors (adjusted ORs = 2.8, 95% CI: 1.3-6.2). These results showed strong dose-response relationships (p for trend = 0.0050). Our findings suggest that historical methylmercury exposure might cause functional impairment in later in life depending on the exposure level.

[Gender differences in the relationship between sleep and depression among elderly people residing at home].

OBJECTIVES: To investigate gender differences in the relationship between sleep and depression in the elderly. METHODS: Residents of a village in Kumamoto Prefecture, Japan (563 people) aged > or =65 years were given a self-administered questionnaire survey between June and July 2010. To evaluate levels of sleep and depression, the Pittsburgh Sleep Quality Index (PSQI) and the Geriatric Depression Scale-Short Form (GDS-SF) were used. Adjustment factors assessed age, income, residence status, social role, medical history, nursing situation, and cognitive function. As with previous studies, respondents were evaluated as having a disturbed sleep or depression if the sum of their PSQI and GDS-SF scores was 6 or more. We examined the relationship between sleep and depression using multiple logistic regression analysis, with presence of depression in each gender introduced as a dependent variable. Given that some degree of correlation was expected among adjustment factors in the model, we constructed a model that introduced the adjustment factors stepwise to confirm the robustness of the model and any effect of multicollinearity. RESULTS: Overall (n=424), a significant relationship was found between disturbed sleep and depression in all models. The odds ratio was 1.92 (95% confidence interval: 1.11-3.32) in the final model, controlling all adjustment factors. In men (n=198), although the relationship between disturbed sleep and depression was significant before adjustment, no significance was observed after adjustment. In women (n=226), however, a significant relationship was observed between disturbed sleep and depression in both models. After the introduction of all variables as adjustment factors, the odds ratio was 2.28 (95% confidence interval: 1.11-4.69). CONCLUSION: Our findings suggest a significant relationship between disturbed sleep and depression in elderly women, but not in men. While the reasons for this gender difference are unclear at present, various factors, such as the endocrine system, are likely to be involved. Future studies should take this gender difference into account in order to enact more effective measures for preventing depression in the elderly.

[Association between depression and fall risk among elderly community residents].

AIM: To investigate the relationship between depression and fall risk in the elderly. METHODS: Residents of a village in Kumamoto Prefecture, Japan (563 people), aged ≥65 years were given a self-administered questionnaire survey between June and July 2010. To evaluate depression status and fall risk, the Geriatric Depression Scale--Short Form and the Simple Screening Test for Risk of Falls were administered. Adjustment factors assessed were age, sex, medical history for diseases associated with falls, usage of hypnotics, and cognitive dysfunction. We examined the relationship between depression and fall risk using multiple logistic regression analysis. Given that some degree of correlation was expected among adjustment factors in the model, we constructed a model that introduced the adjustment factors stepwise to confirm the robustness of the model and any effect of multicollinearity. RESULTS: Overall (n=395), after excluding data from participants with significant cognitive disturbance or severe physical problems from among valid responders, a significant relationship was found between depression and fall risk in all models. The odds ratio was 2.28 (95% confidence interval: 1.31-3.96) in the final model, controlling for all adjustment factors. CONCLUSION: Our findings suggest a significant relationship between depression and fall risk in the elderly. This relationship implies that the improvement of depression could be an effective measure to decrease fall risk in the elderly.

Transient Astrocytic Gq Signaling Underlies Remote Memory Enhancement.

Astrocytes elicit transient Ca2+ elevations induced by G protein-coupled receptors (GPCRs), yet their role in vivo remains unknown. To address this, transgenic mice with astrocytic expression of the optogenetic Gq-type GPCR, Optoα1AR, were established, in which transient Ca2+ elevations similar to those in wild type mice were induced by brief blue light illumination. Activation of cortical astrocytes resulted in an adenosine A1 receptor-dependent inhibition of neuronal activity. Moreover, sensory stimulation with astrocytic activation induced long-term depression of sensory evoked response. At the behavioral level, repeated astrocytic activation in the anterior cortex gradually affected novel open field exploratory behavior, and remote memory was enhanced in a novel object recognition task. These effects were blocked by A1 receptor antagonism. Together, we demonstrate that GPCR-triggered Ca2+ elevation in cortical astrocytes has causal impacts on neuronal activity and behavior.

Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice.

Reduced expression of glutamate decarboxylase 67 (GAD67), encoded by the Gad1 gene, is a consistent finding in postmortem brains of patients with several psychiatric disorders, including schizophrenia, bipolar disorder and major depressive disorder. The dysfunction of GAD67 in the brain is implicated in the pathophysiology of these psychiatric disorders; however, the neurobiological consequences of GAD67 dysfunction in mature brains are not fully understood because the homozygous Gad1 knockout is lethal in newborn mice. We hypothesized that the tetracycline-controlled gene expression/suppression system could be applied to develop global GAD67 knockdown mice that would survive into adulthood. In addition, GAD67 knockdown mice would provide new insights into the neurobiological impact of GAD67 dysfunction. Here, we developed Gad1tTA/STOP-tetO biallelic knock-in mice using Gad1STOP-tetO and Gad1tTA knock-in mice, and compared them with Gad1+/+ mice. The expression level of GAD67 protein in brains of Gad1tTA/STOP-tetO mice treated with doxycycline (Dox) was decreased by approximately 90%. The GABA content was also decreased in the brains of Dox-treated Gad1tTA/STOP-tetO mice. In the open-field test, Dox-treated Gad1tTA/STOP-tetO mice exhibited hyper-locomotor activity and decreased duration spent in the center region. In addition, acoustic startle responses were impaired in Dox-treated Gad1tTA/STOP-tetO mice. These results suggest that global reduction in GAD67 elicits emotional abnormalities in mice. These GAD67 knockdown mice will be useful for elucidating the neurobiological mechanisms of emotional abnormalities, such as anxiety symptoms associated with psychiatric disorders.