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Nerve/glial antigen 2 (NG2) is a protein marker of NG2 glia and mural cells, and NG2 promoter activity is utilized to target these cells. However, the NG2 promoter cannot target NG2 glia and mural cells separately. This has been an obstacle for NG2 glia-specific manipulation. Here, we developed transgenic mice in which either cell type can be targeted using the NG2 promoter. We selected a tetracycline-controllable gene induction system for cell type-specific transgene expression, and generated NG2-tetracycline transactivator (tTA) transgenic lines. We crossed tTA lines with the tetO-ChR2 (channelrhodopsin-2)-EYFP line to characterize tTA-dependent transgene induction. We isolated two unique NG2-tTA mouse lines: one that induced ChR2-EYFP only in mural cells, likely due to the chromosomal position effect of NG2-tTA insertion, and the other that induced it in both cell types. We then applied a Cre-mediated set-subtraction strategy to the latter case and eliminated ChR2-EYFP from mural cells, resulting in NG2 glia-specific transgene induction. We further demonstrated that tTA-dependent ChR2 expression could manipulate cell function. Optogenetic mural cell activation decreased cerebral blood flow, as previously reported, indicating that tTA-mediated ChR2 expression was sufficient to impact cellular function. ChR2-mediated depolarization was observed in NG2 glia in acute hippocampal slices. In addition, ChR2-mediated depolarization of NG2 glia inhibited their proliferation but promoted their differentiation in juvenile mice. Since the tTA-tetO combination is expandable, the mural cell-specific NG2-tTA line and the NG2 glia-specific NG2-tTA line will permit us to conduct observational and manipulation studies to examine in vivo function of these cells separately., (© 2022 Wiley Periodicals LLC.)

In hippocampal CA1 neurons of wild-type mice, a short tetanus (15 or 20 pulses at 100 Hz) or a standard tetanus (100 pulses at 100 Hz) to a naive input pathway induces long-term potentiation (LTP) of the responses. Low-frequency stimulation (LFS; 1000 pulses at 1 Hz) 60 min after the standard tetanus reverses LTP (depotentiation [DP]), while LFS applied 60 min prior to the standard tetanus suppresses LTP induction (LTP suppression). We investigated LTP, DP, and LTP suppression of both field excitatory postsynaptic potentials and population spikes in CA1 neurons of mice lacking the inositol 1,4,5-trisphosphate (IP 3 ) receptor (IP 3 R)-binding protein released with IP 3 (IRBIT). The mean magnitudes of LTP induced by short and standard tetanus were not different in mutant and wild-type mice. In contrast, DP and LTP suppression were attenuated in mutant mice, whereby the mean magnitude of responses after LFS or tetanus were significantly greater than in wild-type mice. These results suggest that, in hippocampal CA1 neurons, IRBIT is involved in DP and LTP suppression, but is not essential for LTP. The attenuation of DP and LTP suppression in mice lacking IRBIT indicates that this protein, released during or after priming stimulations, determines the direction of LTP expression after the delivery of subsequent stimulations., (© 2022 Goto et al.; Published by Cold Spring Harbor Laboratory Press.)

This study examined the relationship between the sense of coherence (SOC), which is conceptually the ability to successfully cope with stress, of Japanese junior high school students and their mothers, and investigated SOC-related factors among the students. We analyzed self-reported data from 134 junior high school students (aged 12-14 years) and their mothers (average age: 45.5 ± 4.1 years), based in an urban area of Japan. We found a weak correlation between the SOC total scores of female students and their mothers; further, few subscales showed weak correlations. However, the SOC of male students was not correlated with that of their mothers, including the three subcomponents that constitute the SOC. The results of multiple regression analysis indicated that the SOC of female students was negatively associated with ASD-related characteristics, sensitivity to evaluation, and avoidant help-seeking style, and positively associated with a sense of belonging to the school. However, male students' SOC showed a negative relationship with excessive response to evaluation and a strong sense of parental control. To improve SOC in adolescents, it is necessary to consider their gender differences and support them, both at home and school., (© 2022. The Author(s).)

We conducted a longitudinal study to clarify the changes in the sense of coherence (SOC); that is, the ability to cope with stress successfully, of 166 Japanese junior high school students and their mothers before and after the onset of the COVID-19 pandemic. First, we analyzed changes in SOC at three time points for all students and divided them into two groups: Group 1 included students with SOC scores that increased or maintained before and after the onset of the pandemic and Group 2 included students with decreased SOC scores after the onset of the pandemic. Second, we conducted a comparative analysis between the two groups. Overall, results indicated that student's SOC scores increased. Additionally, interpersonal stress scores were lower after the onset of the pandemic than before. There were almost no differences in family relationships, financial conditions, or personality tendencies between the two groups. However, Group 2 did not regain their sense of belonging to school. In this group, the frequency of stress experiences in club activities after the onset of the pandemic, troubles with the opposite gender, and inability to catch up with the contents of the subject lecture were high. The accumulation of small stressors may have hindered the maintenance of a sense of school affiliation. Mothers of students in Group 2 either were full-time employees at baseline or had started a new job after the onset of the pandemic. Their children may have been affected by the household's damaged financial budget and changes in mother's working styles. As COVID-19 reduced the number of days students went to school, students' SOC could have reduced had they not felt a sense of presence or belonging due to the lack of participation in club activities, school events, etc. Teachers and mothers should communicate carefully with their students and children, respectively, to develop a sense of belonging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Omiya, Deguchi, Sakata, Takata and Yamazaki.)

The juvenile brain presents plasticity. Oligodendrocytes are the myelinating cells of the central nervous system and myelination can be adaptive. Plasticity decreases from juvenile to adulthood. The mechanisms involving oligodendrocytes underlying plasticity are unclear. Here, we show Na + -K + -Cl - co-transporter 1 (NKCC1), highly expressed in the juvenile mouse brain, regulates the oligodendrocyte activity from juvenile to adulthood in mice, as shown by optogenetic manipulation of oligodendrocytes. The reduced neuronal activity in adults was restored by Nkcc1 overexpression in oligodendrocytes. Moreover, in adult mice overexpressing Nkcc1, long-term potentiation and learning were facilitated compared to age-matched controls. These findings demonstrate that NKCC1 plays a regulatory role in the age-dependent activity of oligodendrocytes, furthermore inducing activation of NKCC1 in oligodendrocytes can restore neuronal plasticity in the adult mouse brain., (© 2021. The Author(s).)

Objectives　To develop and assess the reliability and validity of a scale measuring subjective quality of life (QOL), which encompasses the "strength and ability" to live positively through the three dimensions of biological life, everyday life, and overall course of life, in order to support QOL in older adults.Methods　We reviewed related literature and conducted interviews with patients with chronic diseases. Participants rated their QOL on a seven-point scale using the visual analog scale. Interviewer-administered questionnaires were used to collect data from 100 older adults living in their own homes. The participants were between the ages of 70 and 84, and were recruited from comprehensive community support centers or from among hospital outpatients. We assessed scale reliability using Cronbach's α, item-total (I-T) correlation analysis, and calculation of α coefficient-if-item-deleted. We examined content validity by analyzing the content of the free response items. To evaluate construct validity, we carried out a hierarchical multiple regression analysis, examined the semantic content of the factors related to subjective QOL, and confirmed consistency with previous studies.Results　Regarding the reliability analysis of the scale, the α coefficient was 0.898, and both the I-T correlation and α coefficient-if-item-deleted exceeded the minimum value considered reliable. In examining content validity, the categories extracted for each of the three dimensions were found to demonstrate the characteristics of the general ideas of each dimension of QOL. Thus, the scale was confirmed to have overall content validity. As for the assessment of validity of its constitutive concepts, subjective QOL scores were significantly high among participants who had jobs, had role-related or financial capacity, used two or more nursing services, or scored high in perceived health competence, social networking, and sense of coherence (SOC). In addition, "meaningfulness" of SOC, and financial capacity had significant correlations with subjective QOL. These results are consistent with past research and therefore confirm construct validity.Conclusion　This study sufficiently confirmed the reliability and validity of the scale, and consequently its usability.

Personal recovery is a process of developing new meaning and purpose in life beyond the catastrophic effects of mental illness. Benefit finding (BF) is conceptualized as finding positive changes or benefits through experiences in adversity. Sense of coherence (SOC) focuses on how people can stay healthy and maintain well-being, even in adversity. This study aimed to examine the relationships among the initial levels and longitudinal changes in personal recovery, BF, and SOC among people with chronic mental illness in Japan. In this longitudinal study, a two-wave self-report questionnaire survey was conducted for service users aged 20 or older with mental illness using convenience sampling method in 2014 and 2015. We applied the Latent Change Score approach. Model fit was evaluated according to the CFI and RMSEA. Among 373 eligible participants at baseline, valid responses in both T1 and T2 from 195 respondents were included in the study (valid response rate = 52.3%). Among them, 65.6% were male, with average age of 45.6. The model of the three constructs at the two time points had good to reasonable fit to the data. The initial levels and changes in personal recovery, BF, and SOC were significantly and positively related to each other.

Benefit finding has been defined as positive life changes that result from a stressful event, such as the diagnosis of chronic illness. The present study aimed to develop a benefit finding questionnaire (BFQ) and examine its psychometric property among people with chronic mental illness in Japan. This study adopted a mixed method composed of three phases, including Phase 1: To draft the item pool and design the BFQ based on literature review and discussion among the authors, Phase 2: To revise and refine the drafted items through feedback from focus group interviews and further consideration, and Phase 3: To examine the psychometric properties of the BFQ following the questionnaire survey for people with chronic mental illness and validation of the questionnaire. In Phase 3, a cross-sectional, self-administered questionnaire survey was conducted for mental health service users. Among the 373 eligible participants, we used data from 265 respondents for the analyses (valid response rate = 71.0%). About 65% were male, and the average age was 45.3 years (SD = 12.9). Around 70% were diagnosed with schizophrenia. Factorial, concurrent, and divergent validities, as well as reliability were explored. The 21-item BFQ demonstrated good factorial validity, concurrent and divergent validities, and sufficient internal consistency reliability among people with chronic mental illness. It appears to be a useful scale to assess experience of benefit finding among people with chronic mental illness. Further large-scale research will ensure verification of the scale among people with other illnesses or difficulties.

Adolescence is marked by significant life stress. Recently, school refusal and dropouts as well as suicide among Japanese adolescents have increased. Sense of coherence (SOC) is recognized as a competency that helps people deal with stress. The purpose of this study was to examine the factors influencing SOC in male and female high school students. We conducted a survey with 203 pairs of high school students and their mothers, in Tokyo, to explore their SOC, family relationships, school belonging, and autistic traits. Analysis of the data revealed a weak relationship between female students' SOC and that of their mothers, and no relationship between male students' SOC and their mothers' SOC. Feelings of acceptance and recognition from teachers improved students' SOC, irrespective of gender. Low SOC in mothers had a negative impact on female students' SOC, and children's lack of imagination (an autism spectrum tendency) had a negative impact on male students' SOC. This study revealed the importance of support at home and school according to the needs of both genders.

In CA1 neurons of guinea pig hippocampal slices, long-term potentiation (LTP) was induced in field excitatory postsynaptic potentials (EPSPs) or population spikes (PSs) by the delivery of high-frequency stimulation (HFS, 100 pulses at 100 Hz) to CA1 synapses, and was reversed by the delivery of a train of low-frequency stimulation (LFS, 1000 pulses at 2 Hz) at 30 min after HFS (depotentiation), and this effect was inhibited when test synaptic stimulation was halted for a 19-min period after HFS or for a 20-min period after LFS or applied over the same time period in the presence of an antagonist of N-methyl-D-aspartate receptors (NMDARs), group I metabotropic glutamate receptors (mGluRs), or inositol 1, 4, 5-trisphosphate receptors (IP 3 Rs). Depotentiation was also blocked by the application of a Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) inhibitor or a calcineurin inhibitor applied in the presence of test synaptic input for a 10-min period after HFS or for a 20-min period after LFS. These results suggest that, in postsynaptic neurons, the coactivation of NMDARs and group I mGluRs due to sustained synaptic activity following LTP induction results in the activation of IP 3 Rs and CaMKII, which leads to the activation of calcineurin after LFS and depotentiation of CA1 synaptic responses., (© 2020 Fujii et al.; Published by Cold Spring Harbor Laboratory Press.)

To investigate how having a child without a disability is related to maternal mental health and its predictors, we compared mothers of a single child with intellectual disabilities (single-child group, n = 117) and mothers of children with and without intellectual disabilities (multiple-children group, n = 457), in Japan. Compared to the multiple-children group, the single-child group had lower hope and social capital and poorer mental health; furthermore, 42.5% of them had decided not to have another child, despite desiring one. Hope was the strongest predictor of mental health in both groups but was more positively related to mental health in the multiple-children group. The fear of the possibility of the next child having a disability and receiving inadequate support were the obstacles for mothers who had decided not to have another child. Thus, greater support and more opportunities for obtaining adequate information about the implications of having another child may be needed.

The axonal conduction of action potentials affects the absolute time it takes to transmit nerve impulses as well as temporal summation at destination synapses. At the physiological level, oligodendrocyte depolarization facilitates axonal conduction along myelinated fibers in the hippocampus; however, the functional significance of this facilitation is largely unknown. In this study, we examined the physiology of the facilitation of axonal conduction by investigating the changes in synaptic responses at destination synapses using male and female mice in which channelrhodopsin-2 expression was restricted to oligodendrocytes. The subiculum, one of the projection areas of the examined axons at the alveus of the hippocampus, is divided into three regions (proximal, mid, and distal) and contains two types of principal neurons: regular firing and bursting pyramidal cells. We found a significant increase in excitatory synaptic responses following optogenetic oligodendrocyte depolarization in bursting neurons at two of the three regions, but not in regular firing neurons at any region. The long-term potentiation (LTP) induced by theta burst stimulation at the synapses showing a significant increase was also enhanced after oligodendrocyte depolarization. Conversely, the reduction of oligodendrocyte depolarization during theta burst stimulation, which was achieved by photostimulation of archaerhodopsin-T expressed selectively on oligodendrocytes, reduced the magnitude of LTP. These results show that oligodendrocyte depolarization contributes to the fine control of synaptic activity between the axons they myelinate and targets subicular cells in a region- and cell type-specific manner, and suggest that oligodendrocyte depolarization during conditioning of stimuli is involved in the induction of LTP. SIGNIFICANCE STATEMENT All activity in the nervous system depends on the propagation of action potentials. Changes in the axonal conduction of action potentials influence the timing of synaptic transmission and information processing in neural circuits. At the physiological level, oligodendrocyte depolarization facilitates axonal conduction along myelinated fibers. In this study, we investigated the functional significance of the facilitation of axonal conduction induced by physiological oligodendrocyte depolarization. Using optogenetics and electrophysiological recordings, we demonstrated that oligodendrocyte depolarization in mice expressing channelrhodopsin-2 on oligodendrocytes increased excitatory synaptic responses and enhanced the induction of long-term potentiation at destination synapses in a region- and cell type-specific manner. This facilitation may have a hitherto unappreciated influence on the transfer of information between regions in the nervous system., (Copyright © 2019 the authors.)

Oligodendrocytes enable saltatory conduction by forming a myelin sheath around axons, dramatically boosts action potential conduction velocity. In addition to this canonical function of oligodendrocytes, it is now known that oligodendrocytes can respond to neuronal activity and regulate axonal conduction. Importantly, white matter plasticity, including adaptive responses by oligodendrocytes, has been shown to be involved in learning and memory. In this chapter, the role of oligodendrocytes in axonal conduction and axonal excitability will be reviewed. Focus will be paid to the mechanisms through which oligodendrocytes, including perineuronal oligodendrocytes, facilitate and suppress axonal conduction.

Mlc1 is a causative gene for megalencephalic leukoencephalopathy with subcortical cysts, and is expressed in astrocytes. Mlc1-over-expressing mice represent an animal model of early-onset leukoencephalopathy, which manifests as astrocytic swelling followed by myelin membrane splitting in the white matter. It has been previously reported that Mlc1 is highly expressed in Bergmann glia, while the cerebellar phenotypes of Mlc1-over-expressing mouse have not been characterized. Here, we examined the cerebellum of Mlc1-over-expressing mouse and found that the distribution of Bergmann glia (BG) was normally compacted along the Purkinje cell (PC) layer until postnatal day 10 (P10), while most BG were dispersed throughout the molecular layer by P28. Ectopic BG were poorly wrapped around somatodendritic elements of PCs and exhibited reduced expression of the glutamate transporter glutamate-aspartate transporter. Extraordinarily slow and small climbing fiber (CF)-mediated excitatory post-synaptic currents, which are known to be elicited under accelerated glutamate spillover, emerged at P20-P28 when BG ectopia was severe, but not at P9-P12 when ectopia was mild. Furthermore, maturation of CF wiring, which translocates the site of innervation from somata to proximal dendrites, was also impaired. Manipulations that restricted the Mlc1-over-expressing period successfully generated mice with and without BG ectopia, depending on the over-expressing period. Together, these findings suggest that there is a critical time window for mechanisms that promote the positioning of BG in the PC layer. Once normal positioning of BG is affected, the differentiation of BG is impaired, leading to insufficient glial wrapping, exacerbated glutamate spillover, and aberrant synaptic wiring in PCs. Open Practices Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/ Cover Image for this issue: doi: 10.1111/jnc.14199., (© 2018 International Society for Neurochemistry.)

Background: To improve and support medication adherence among patients with chronic diseases, especially for long-term medication, it is important to consider both their relationship with healthcare providers and their lifestyle. We tested the reliability and validity of a modified 12-item Medication Adherence Scale., Methods: We revised a 14-item measure of medication adherence, created in 2009, to a more concise and clear 12-item version, and we verified the reliability and validity of the 12-item scale. We included 328 patients with chronic diseases participating in the Chronic Disease Self-Management Program in Japan from 2011 to 2014. Confirmatory factor analysis was used to assess whether the four factors assessed were the same as the previous 14-item Medication Adherence Scale. Cronbach's coefficient alpha was used to assess internal consistency reliability, and the relationships between patient demographic characteristics and medication adherence were compared with previous studies., Results: The 12 items were categorized into the four factors "medication compliance", "collaboration with healthcare providers", "willingness to access and use information about medication", and "acceptance to take medication and how taking medication fits patient's lifestyle". Confirmatory factor analysis showed χ 2 /df = 2.6, CFI = 0.94, and RMSEA = 0.069. Cronbach's alpha for the 12-item scale was 0.78. Cronbach's alpha for the four subscales was 0.74, 0.81, 0.67, and 0.45. Higher medication adherence was significantly associated with being a female patient, living with someone else, and age 40-49 years versus age 20-29 years. These relationships were the same as in previous studies., Conclusions: We modified our original 14-item scale to a 12-item Medication Adherence Scale for patients with chronic diseases, which considers their relationship with healthcare providers and lifestyle. Refinement might be needed because of the relatively low reliability of subscales. However, the modified scale is expected to contribute to more effective self-management of medication and to improving medication adherence, particularly among patients with chronic diseases who require long-term medication not only in Japan but also in other countries.

Aim: The purpose was to characterize public perceptions in Japan of mental illness and how they related to stigma-related attitudes for the same., Methods: Data were obtained using a vignette survey conducted as a part of the Stigma in Global Context - Mental Health Study and contained a nationally representative sample (n = 994). The survey was conducted using a multi-mode approach (face-to-face interviews, the drop-off-and-pick-up, postal collection) from September to December 2006, with a multi-stage probability sample of Japanese residents aged 18-64 years. Respondents were randomly assigned one of four vignette conditions that described psychiatric disorders meeting the diagnostic criteria for schizophrenia and major depressive disorder (one vignette for each gender exhibiting each diagnosis). We compared respondents' stigma-related attitudes and perceptions toward mental illness between vignettes., Results: Over 80% of Japanese participants believed that depressive disorder or schizophrenia could be cured via treatment. However, Japanese people still had relatively strong vigilance and denial of competency toward schizophrenia., Conclusions: Participants expressed the belief that mental illnesses are curable, but stigma toward people with schizophrenia was still relatively strong., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Action potentials are fundamental to relaying information from region to region in the nervous system. Changes in action potential firing patterns in neural circuits influence how the brain processes information. In our previous study, we focused on interneuron/perineuronal astrocyte pairs in the hippocampal CA1 region and reported that direct depolarization of perineuronal astrocytes modulated the firing pattern of interneurons. In the current study, we investigated the morphological and electrophysiological properties of perineuronal oligodendrocytes, and examined their modulatory effects on interneuronal firing in the CA1 region. Perineuronal oligodendrocytes only had a few processes, which were crooked, intricately twisted, and twined around the soma and proximal region of the main processes of adjacent interneurons. Whole-cell current patterns of perineuronal oligodendrocytes were homogenous and the current-voltage relationship showed remarkable outward rectification. Although the K + channel blockers, tetraethylammonium and 4-aminopyridine, clearly blocked outward currents, Ba 2+ did not significantly alter whole-cell currents. Unlike perineuronal astrocytes, the depolarization of perineuronal oligodendrocytes had no effect on interneuronal firing; however, when the interneurons were firing at a higher frequency, the hyperpolarization of perineuronal oligodendrocytes suppressed their action potentials. The suppressive effects of perineuronal oligodendrocytes were inhibited in the presence of a low concentration of tetraethylammonium, which selectively blocked deep and fast afterhyperpolarization. These results suggest that perineuronal oligodendrocytes suppress interneuronal firing through their influence on K + channels, which are responsible for deep and fast afterhyperpolarization.

The purpose of this study was to clarify the factors related to perceived positive change and sense of coherence in mothers ( n  = 293) of children with cleft lip and palate. The strongest negative correlation with sense of coherence was stigmatizing words from others; there were positive correlations with social capital and perceived positive change. Multiple regression showed that to be aware of positive changes, mothers share their feelings with mothers in the same position, are rooted in a safe community and do not feel isolated in parenting. People who have experienced adversity may have the opportunity to enhance sense of coherence by obtaining perceived positive change., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

A high rate of heavy tobacco smoking among people with schizophrenia has been suggested to reflect self-medication and amelioration of cognitive dysfunction, a core feature of schizophrenia. NMDAR hypofunction is hypothesized to be a mechanism of cognitive dysfunction, and excessive schizophrenia-linked neuregulin 1 (NRG1) signaling through its receptor ErbB4 can suppress NMDAR function by preventing Src-mediated enhancement of NMDAR responses. Here we investigated whether chronic nicotine exposure in rats by subcutaneous injection of nicotine (0.5-1 mg/kg, twice daily for 10-15 days) counteracts the suppressive effect of NRG1β on NMDAR-mediated responses recorded from CA1 pyramidal cells in acute hippocampal slices. We found that NRG1β, which prevents the enhancement of NMDAR responses by the Src-family-kinase-activating peptide pYEEI in naive rats, failed to block the effect of pYEEI in nicotine-exposed rats. In naive rats, NRG1β acts only on GluN2B-NMDARs by blocking their Src-mediated upregulation. Chronic nicotine exposure causes enhanced GluN2B-NMDAR responses via Src upregulation and recruits Fyn for the enhancement of GluN2A-NMDAR responses. NRG1β has no effect on both enhanced basal GluN2B-NMDAR responses and Fyn-mediated enhancement of GluN2A-NMDAR responses. Src-mediated enhancement of GluN2B-NMDAR responses and Fyn-mediated enhancement of GluN2A-NMDAR responses initiate long-term potentiation (LTP) of AMPAR synaptic responses in naive and nicotine-exposed CA1 pyramidal cells, respectively. These results suggest that NRG1β suppresses LTP by blocking Src-mediated enhancement of GluN2B-NMDAR responses, but has no effect on LTP in nicotine-exposed rats. These effects of chronic nicotine exposure may counteract the negative effect of increased NRG1-ErbB4 signaling on the cellular mechanisms of learning and memory in individuals with schizophrenia, and therefore may motivate heavy smoking., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We investigated predictors of mental health and positive change among mothers of children with intellectual disabilities in Japan based on the concept of the Double ABCX model. We used variables of having a child with autism spectrum disorder (ASD) and dissatisfaction with systems as stressors, availability of social support and social capital (SC) as existing resources, sense of coherence (SOC) as appraisal of the stressor, and mental health and positive change as adaptation. A self-administered questionnaire was distributed to 10 intellectual disability-oriented special needs schools in Tokyo, and obtained 613 responses from mothers of children under age 20 attending these schools. The results showed that our Double ABCX model explained 46.0% of the variance in mothers' mental health and 38.9% of the variance in positive change. The most powerful predictor of this model was SOC, and SC may be directly and indirectly related to maternal mental health and positive change through mothers' SOC. Increasing opportunity for interaction between neighbors and family of children with disabilities may be one effective way to enhance SOC through SC. Since maternal SOC, SC, mental health, and positive change were significantly correlated with each other, synergy among these elements could be expected., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The neuromodulator acetylcholine (ACh) is considered to have a crucial effect on sensory inputs in the process of learning and memory, and ACh activates muscarinic (mAChR) and nicotinic (nAChR) acetylcholine receptors. Meanwhile in a hippocampal CA1 network including inhibitory connections, long-term potentiation (LTP) or long-term depression (LTD) is induced by the application of positive timing of the spike timing-dependent plasticity (STDP) protocol, while LTD is induced by negative timing protocol. In the previous study, the influence of ACh on LTD induced by the negative timing protocol application in the interneuron-blocked CA1 network was reported. However, the responsibility of mAChR and nAChR on pyramidal neuron and interneuron on STDP induction is still unclear. In order to clarify the role of AChRs in LTD, positive or negative timing protocol was applied in the interneuron-activated CA1 network in the presence of eserine. Consequently, the LTD induced by the positive timing protocol was switched to LTP, and the LTD by negative timing protocol was shifted toward potentiation when ACh was effective. The STDP facilitation was more effectively brought by mAChR activation on pyramidal neuron than nAChR, while mAChR on interneuron had a potential to down regulate the facilitation. These findings suggest that the direction (LTD/LTP) of STDP is determined by the activation of mAChR not only on pyramidal neuron but also on interneuron, and the magnitude of STDP is sensitively fine-tuned by nAChR. Therefore, the modulation of synaptic plasticity induced by the coactivation of mAChR and nAChR might be an important stage in integrating ACh and sensory inputs in the hippocampal CA1 network., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Although sense of coherence (SOC) moderates parental stress, the relationship between SOC, parental mental health and physical punishment of children with intellectual disabilities remains uncertain. The present authors describe parental physical punishment towards children with intellectual disabilities and investigate its related demographic characteristics, SOC and parental mental health., Materials and Methods: With the cooperation of Tokyo's 10 special needs schools, the present authors obtained 648 questionnaire responses from parents of children with intellectual disabilities., Results: Of the parents, 69.7% reported having physically punished their children with intellectual disabilities. This was positively associated with parents' younger age, poorer mental health, lower SOC, children's younger age, birth order (firstborns) and disability type (autism/pervasive developmental disorder)., Conclusions: This is the first study supporting the relationship between SOC, mental health and physical punishment use among parents of children with intellectual disabilities. It may assist the development of strategies to prevent physical abuse of children with disabilities., (© 2015 John Wiley & Sons Ltd.)

The long-term potentiation (LTP) in the field excitatory postsynaptic potential (EPSP) induced at hippocampal CA1 pyramidal neuron synapses by delivery of high frequency stimulation (HFS), a tetanus of 100 pulses at 100Hz, is decreased (depotentiation) by a train of low frequency stimulation (LFS) of 1000 pulses at 2Hz applied 30min later. Inositol 1, 4, 5-trisphosphate receptors (IP3Rs) activated both during the HFS and after the LFS are involved in this depotentiation, the former triggering, and the latter modifying, LTP induction (decreasing the amplitude of the LTP established by the priming HFS). Furthermore, the decrease in the LTP at CA1 synapses requires activation of IP3Rs during LFS and activation of calcineurin after LFS. These results suggest that, at hippocampal CA1 neuron synapses, HFS-induced IP3R activation, which is modulated by the subsequent LFS, results in postsynaptic protein dephosphorylation after the LFS, leading to a decrease in the field EPSP and in the HFS-induced LTP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We investigated the role of inositol 1,4,5-trisphosphate receptors (IP3Rs) activated by preconditioning low-frequency afferent stimulation (LFS) in the subsequent induction of long-term potentiation (LTP) in CA1 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential or the population spike by the delivery of high-frequency stimulation (HFS, a tetanus of 100 pulses at 100 Hz) to the Schaffer collateral-commissural pathway to CA1 neuron synapses was suppressed when group I metabotropic glutamate receptors (mGluRs) were activated prior to the delivery of HFS. LTP induction was also suppressed when CA1 synapses were preconditioned 60 min before HFS by LFS of 1000 pulses at 1 Hz and this effect was inhibited when the test stimulation delivered at 0.05 Hz was either halted or applied in the presence of an antagonist ofN-methyl-d-aspartate receptors, group I mGluRs, or IP3Rs during a 20-min period from 20 to 40 min after the end of LFS. Furthermore, blockade of group I mGluRs or IP3Rs immediately before the delivery of HFS overcame the effects of the preconditioning LFS on LTP induction. These results suggest that, in CA1 neurons, after a preconditioning LFS, activation of group I mGluRs caused by the test stimulation results in IP3Rs activation that leads to a failure of LTP induction., (© 2016 Fujii et al.; Published by Cold Spring Harbor Laboratory Press.)

Synaptic plasticity is believed to be a cellular mechanism for memory formation in the brain. It has been known that the metabotropic glutamate receptor (mGluR) is required for persistent forms of memory and induction of synaptic plasticity. Application of mGluR agonists induces synaptic plasticity in the absence of electrical conditioning stimulation, such as high or low frequency stimulation. The direction of the mGluR-induced synaptic plasticity, i.e., either long-term potentiation (LTP) or long-term-depression (LTD), is dependent on whether N-methyl-D-aspartate receptors (NMDARs) are co-activated with mGluRs. ATP has modulatory effects on neuronal functions and, in particular, there is increasing evidence that it plays a crucial role in synaptic plasticity. LTP can be induced by application of ATP, and this effect is inhibited by NMDAR antagonist. Although cooperative effects of NMDARs and mGluRs and of NMDARs and extracellular ATP in synaptic plasticity have been revealed, the effect of extracellular ATP on mGluR-induced synaptic plasticity is unknown. In this article, we summarize published data on mGluR- and ATP-induced synaptic plasticity, and present new data showing that extracellular ATP facilitates both the LTP and LTD induced by mGluR activation.

The axonal conduction of action potentials in the nervous system is generally considered to be a stable signal for the relaying of information, and its dysfunction is involved in impairment of cognitive function. Recent evidence suggests that the conduction properties and excitability of axons are more variable than traditionally thought. To investigate possible changes in the conduction of action potentials along axons in the central nervous system, we recorded action potentials from granule cells that were evoked and conducted antidromically along unmyelinated mossy fibers in the rat hippocampus. To evaluate changes in axons by eliminating any involvement of changes in the somata, two latency values were obtained by stimulating at two different positions and the latency difference between the action potentials was measured. A conditioning electrical stimulus of 20 pulses at 1 Hz increased the latency difference and this effect, which lasted for approximately 30 s, was inhibited by the application of an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist or a GluK1-containing kainate receptor antagonist, but not by an AMPA receptor-selective antagonist or an N-methyl-d-aspartate receptor antagonist. These results indicated that axonal conduction in mossy fibers is modulated in an activity-dependent manner through the activation of GluK1-containing kainate receptors. These dynamic changes in axonal conduction may contribute to the physiology and pathophysiology of the brain., (© 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objectives: The amount of research relating to evaluation of intervention programs with regard to sense of coherence, a concept of salutogenic stressor coping capacity, is increasing in Japan. However, a nationally representative score of the Japanese version of the sense of coherence scale has not yet been reported. The aim of this study was to describe the 13-item, 7-point Japanese sense of coherence scale (SOC-13), with scoring by sex and age group, and to examine the relationships between the score and locality and city size., Methods: Four thousand Japanese men and women were selected by stratified random sampling, and a cross-sectional, self-administered questionnaire survey was conducted using the placement method. Responses were obtained from 2,067 individuals (response rate: 51.7%). This study analyzed 956 men and 1,107 women (mean age [standard deviation]: 50.0 [14.3])., Results: The mean score on the SOC-13 was 59.0 (12.2) in all participants, 59.1 (11.8) in men, and 58.9 (12.5) in women. No significant difference was found between men and women (P=0.784). ANOVA and multiple comparison for age difference showed a clear relationship (P<0.05) between higher age and a higher SOC-13 score. Moreover, the results of main and interaction effects in ANCOVA, with independent variables for locality (11 segments) and city size (four segments), were not significant when controlled for age., Conclusion: A nationally representative score for the Japanese SOC-13 was acquired. In future research, application of the SOC-13 in Japan for clinical studies is anticipated based on the nationally representative score.

Background: The present study investigated when and how Japanese people with cleft lip and palate (CL/P) learn that their condition is congenital; the perceived effects of withholding the CL/P diagnosis on patients; and whether the resulting social experience and self-esteem are related. A questionnaire survey was conducted in 71 adults with CL/P recruited through a hospital, a patients' association, and by snowball sampling., Results: The participants became aware of their physical difference in childhood, but many reported difficulty in understanding their condition. Participants reported that their families avoided the topic of diagnosis. Participants who understood their condition during childhood rather than in adulthood were significantly more likely to consider this scenario as positive (p < 0.001). Although stigmatising experiences were extremely painful, most patients hid their suffering, making it more difficult to obtain social support. Participants with high self-esteem were more likely to feel that they received adequate support., Conclusions: It is important to explain the congenital nature of CL/P sufficiently and early. In addition, openness by the family about the diagnosis, rather than avoidance, may improve patients' self-esteem. Sufficient support from family, health care providers, and significant others is needed for patients to develop adequate self-esteem.

Astrocytes regulate the activity of neighboring neurons by releasing chemical transmitters, including ATP. Adenosine levels in the cerebrospinal fluid of mice that express a mutant human glial fibrillary acidic protein in astrocytes are slightly elevated compared to those in wild type mice and this might result from the observed increased release by mutant astrocytes of ATP, which can be used to produce adenosine. Using hippocampal slices from these mutant mice, we examined whether the increased endogenous adenosine levels in the hippocampus modulate the reversal of long-term potentiation (LTP), i.e. depotentiation (DP), in CA1 neurons. In hippocampal slices from wild type mice, a stable LTP was induced by tetanic stimulation consisting of 100 pulses at 100 Hz, and this was reversed by a train of low frequency stimulation (LFS) of 500 pulses at 1 Hz applied 30 min later. This induction of DP was inhibited by application of either 100 nM adenosine or 0.5 nM N(6)-cyclopentyladenosine, an adenosine A1 receptor agonist, during LFS, indicating that the increase in extracellular adenosine levels attenuated DP induction by acting on adenosine A1 receptors. In contrast, although a stable LTP was also induced in hippocampal slices from mutant mice, induction of DP was inhibited, but DP could be induced by application, during LFS, of 50 nM 8-cyclopentyltheophylline, an adenosine A1 receptor antagonist. These results suggest that a small increase in extracellular adenosine levels resulting from increased ATP release by astrocytes results in attenuation of DP in hippocampal CA1 neurons in the mutant mice., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Nicotinic and muscarinic ACh receptor agonists and acetylcholinesterase inhibitors (AChEIs) can enhance cognitive function. However, it is unknown whether a common signaling pathway is involved in the effect. Here, we show that in vivo administration of nicotine, AChEIs, and an m1 muscarinic (m1) agonist increase glutamate receptor, ionotropic, N-methyl D-aspartate 2B (GluN2B)-containing NMDA receptor (NR2B-NMDAR) responses, a necessary component in memory formation, in hippocampal CA1 pyramidal cells, and that coadministration of the m1 antagonist pirenzepine prevents the effect of cholinergic drugs. These observations suggest that the effect of nicotine is secondary to increased release of ACh via the activation of nicotinic ACh receptors (nAChRs) and involves m1 receptor activation through ACh. In vitro activation of m1 receptors causes the selective enhancement of NR2B-NMDAR responses in CA1 pyramidal cells, and in vivo exposure to cholinergic drugs occludes the in vitro effect. Furthermore, in vivo exposure to cholinergic drugs suppresses the potentiating effect of Src on NMDAR responses in vitro. These results suggest that exposure to cholinergic drugs maximally stimulates the m1/guanine nucleotide-binding protein subunit alpha q/PKC/proline-rich tyrosine kinase 2/Src signaling pathway for the potentiation of NMDAR responses in vivo, occluding the in vitro effects of m1 activation and Src. Thus, our results indicate not only that nAChRs, ACh, and m1 receptors are on the same pathway involving Src signaling but also that NR2B-NMDARs are a point of convergence of cholinergic and glutamatergic pathways involved in learning and memory.

Plastic changes in white matter have received considerable attention in relation to normal cognitive function and learning. Oligodendrocytes and myelin, which constitute the white matter in the central nervous system, can respond to neuronal activity with prolonged depolarization of membrane potential and/or an increase in the intracellular Ca(2+) concentration. Depolarization of oligodendrocytes increases the conduction velocity of an action potential along axons myelinated by the depolarized oligodendrocytes, indicating that white matter shows functional plasticity, as well as structural plasticity. However, the properties and mechanism of oligodendrocyte depolarization-induced functional plastic changes in white matter are largely unknown. Here, we investigated the functional plasticity of white matter in the hippocampus using mice with oligodendrocytes expressing channelrhodopsin-2. Using extracellular recordings of compound action potentials at the alveus of the hippocampus, we demonstrated that light-evoked depolarization of oligodendrocytes induced early- and late-onset facilitation of axonal conduction that was dependent on the magnitude of oligodendrocyte depolarization; the former lasted for approximately 10 min, whereas the latter continued for up to 3 h. Using whole-cell recordings from CA1 pyramidal cells and recordings of antidromic action potentials, we found that the early-onset short-lasting component included the synchronization of action potentials. Moreover, pharmacological analysis demonstrated that the activation of Ba(2+) -sensitive K(+) channels was involved in early- and late-onset facilitation, whereas 4-aminopyridine-sensitive K(+) channels were only involved in the early-onset component. These results demonstrate that oligodendrocyte depolarization induces short- and long-term functional plastic changes in the white matter of the hippocampus and plays active roles in brain functions., (© 2014 Wiley Periodicals, Inc.)

In developed countries, human immunodeficiency virus (HIV) has become a chronic disease. The aims of this study were to clarify the physical, social, and psychological factors affecting Japanese HIV patients in a stable condition and to identify factors related to mental health of employed and unemployed HIV patients. The target subjects were people with HIV infection who were treated as outpatients at core hospitals for acquired immune deficiency syndrome (AIDS) treatment in Japan. A questionnaire including items from the Hospital Anxiety and Depression Scale (HADS) was sent to each medical facility with a request for participation from the HIV-infected outpatients. Responses from 1199 patients were analyzed. Mental health was reportedly better in the employed patients than in the unemployed patients. The unemployed patients were more likely to have resigned from their jobs because of poor health, to have resigned voluntarily, or to have been unfairly dismissed. Once the patients stopped working because of HIV, returning to work became difficult. In the employed patients, a good workplace environment was strongly related to lower scores on HADS. Higher HADS scores were recorded for employed patients infected with HIV for six years or more. For the unemployed patients, a relationship was observed between strong feelings of stigmatization and HADS scores. Quitting a job because of an experience related to HIV status may be related to feelings of stigmatization.

In this study, we explored the lived experience of Japanese mothers who have delivered multiple children with intellectual disabilities (ID), using interpretative phenomenological analysis. We identified three superordinate themes and seven subordinate themes from the narrative data collected from 10 participants. The superordinate themes were: abandoned hope for having an ordinary family, accumulating physical and mental fatigue, and searching for positive experiences in parenting multiple children with disabilities. How they perceived the birth of children with disabilities for the second time differed depending on the disability types; specifically, whether they detected the disabilities early or not. Encountering the disability in another child overwhelmed mothers, especially when the disabilities were diagnosed after several years with or without suspicion; they struggled to accept the fact. Despite mothers facing extreme difficulties in parenting multiple children with disabilities, they tried to alter the negative perceptions and find an optimistic way of living.

Background: In people with chronic illnesses, self-management education can reduce anxiety and depression. Those benefits, however, decay over time. Efforts have been made to prevent or minimize that "decay of impact", but they have not been based on information about the decay's characteristics, and they have failed. Here we show how the decay's basic characteristics (prevalence, timing, and magnitude) can be quantified. Regarding anxiety and depression, we also report the prevalence, timing, and magnitude of the decay., Methods: Adults with various chronic conditions participated in a self-management educational program (n = 369). Data were collected with the Hospital Anxiety and Depression Scale four times over one year. Using within-person effect sizes, we defined decay of impact as a decline of ≥0.5 standard deviations after improvement by at least the same amount. We also interpret the results using previously-set criteria for non-cases, possible cases, and probable cases., Results: Prevalence: On anxiety, decay occurred in 19% of the participants (70/369), and on depression it occurred in 24% (90/369). Timing: In about one third of those with decay, it began 3 months after the baseline measurement (6 weeks after the educational program ended). Magnitude: The median magnitudes of decay on anxiety and on depression were both 4 points, which was about 1 standard deviation. Early in the follow-up year, many participants with decay moved into less severe clinical categories (e.g., becoming non-cases). Later, many of them moved into more severe categories (e.g., becoming probable cases)., Conclusions: Decay of impact can be identified and quantified from within-person effect sizes. This decay occurs in about one fifth or more of this program's participants. It can start soon after the program ends, and it is large enough to be clinically important. These findings can be used to plan interventions aimed at preventing or minimizing the decay of impact.

We studied the synaptic plasticity of hippocampal CA1 neurons and spatial learning behavior in gerbils that had been loaded with a transient cerebral ischemia caused by 5 min or 10 min occlusion of the bilateral carotid arteries. The stimulus threshold to elicit the field responses after a transient cerebral ischemia was not different from that in controls, but there was a significant decrease in the magnitude of synaptic responses, which might result from the observed loss of neurons. Long-term potentiation (LTP) and depotentiation after a 10 min cerebral ischemia expressed as a percentage of the pre-tetanus or pre-low frequency stimulation value were almost the same as those in controls, although the actual magnitude of the LTP and depotentiation was lower than in controls. Gerbils that were loaded with a 10 min cerebral ischemia showed impairment in a spatial learning test when this was started 10 days after the cerebral ischemia, but not when it was started 20 days after the same cerebral ischemia. These results suggest that the changes in electrophysiological properties of hippocampal CA1 neurons seen at 10 days after a 10 min cerebral ischemia contribute to the impairment of spatial learning of gerbils seen at this time, and that the extra-CA1 regions might be involved in the recovery of spatial learning seen at 20 days after cerebral ischemia.

Astrocytes, a major subtype of glia, interact with neurons as a supportive partner supplying energy sources and growth factors. Astrocytes regulate the activity of neighboring neurons by releasing chemical transmitters (gliotransmitters). However, the precise role of gilotransmitters in regulating neuronal activity is still under debate. Here, we report that a subtle enhancement in the release of one gliotransmitter, ATP, affects synaptic potentiation from an analysis of mice containing an astrocyte-selective (GFAP) mutation. We found that, relative to normal mice, weaker stimulation induced long-term potentiation (LTP) in mutant mice, indicating that the threshold to induce LTP was lowered in the mutant. While excitatory transmission was normal in the mutant, inhibitory GABAergic transmission was suppressed. We found that a low concentration of adenosine selectively attenuated inhibitory neuronal activity and lowered the threshold to induce LTP in wild type mice. In comparison, adenosine A(1) receptor antagonism reversed the lowered LTP threshold back to normal in the mutant mouse. We verified that adenosine levels in the cerebrospinal fluid of mutant mice were slightly elevated compared to wild type mice. This was apparently caused by an increase in ATP release from mutant astrocytes that could provide a source of augmented adenosine levels in the mutant. ATP is thought to suppress the excitability of neuronal circuits; however, a small increase in ATP release can result in a suppressed inhibitory tone and enhanced excitability of neuronal circuitry. These findings demonstrate that ATP released from astrocytes acts in a bidirectional fashion to regulate neuronal excitability depending on concentration., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: There is growing recognition that healthcare policy should be guided by the illness experience from a layperson's or insider's perspective. One such area for exploration would include patient-centered research on traumatic Spinal Cord Injury (SCI), a condition associated with permanent physical disability requiring long-term and often complex health care. The chronicity of SCI can, in turn, affect individuals' sense of self. Although previous research in Western countries suggests that people with SCI find a way to cope with their disability through social participation and family bonds, the process of adjustment among people with cervical SCI (CSCI) living in Japan may be different because of the restrained conditions of their social participation and the excessive burden on family caregivers. The purpose of this study was to examine the impact of injury and the process of accommodation in people with CSCI in Japan., Methods: Semi-structured home interviews were conducted with 29 participants who were recruited from a home-visit nursing care provider and three self-help groups. Interviews were recorded, transcribed and analyzed based on the grounded theory approach., Results: Five core categories emerged from the interview data: being at a loss, discrediting self by self and others, taking time in performance, restoring competency, and transcending limitations of disability. Overall, the process by which participants adjusted to and found positive meaning in their lives involved a continuous search for comfortable relationships between self, disability and society., Conclusions: The results of this study suggest that persons with CSCI do not merely have disrupted lives, but find positive meaning through meaningful interactions. Family members added to the discredit of self by making the injured person entirely dependent on them. Gaining independence from family members was the key to restoring competency in people with CSCI. At the same time, social participation was pursued for transcending the limitations of disability. The results also imply that social issues affect how people interpret their disability. These findings suggest that public health policy makers should recognize the need to enhance independence in people with disability as well as change the social assumptions about their care.

Background: The salutogenic model states that coping resources are defined within sociocultural and historical contexts and that various social and historical factors influence the availability of such resources. Though previous studies have suggested the need for an interregional comparison of psychological and social resources, few studies have undertaken such an investigation. The aim of this study is to investigate the associations among coping resources, sense of coherence (SOC), and health status in a comparison of urban and rural residents., Methods: General residents (aged 30-69 years) in two areas were targeted for the current study. Through a random sampling selection, 1,000 residents from each area were picked, and an anonymous questionnaire was mailed to each resident. Ultimately, 269 and 363 valid responses from the urban and rural areas, respectively, were analyzed. SOC, both social and psychological resources, and mental health were assessed. To examine relationships between SOC and resources associated with mental health, mental health was defined as a dependent variable. Hierarchical multiple regression was conducted with variables entered from sociodemographic characteristics, social and psychological resources, and SOC., Results: Regarding regional characteristics, social capital and participation in community activities were significantly greater in the rural area than in the urban area. Urban residents reported significantly higher self-esteem and optimism than rural residents. SOC showed the most significant association with mental health in both areas. Mental health was significantly associated with physical activity limitations and life stressors in both areas. However, the associations were weakened when social and psychological resources and SOC were added, which demonstrated their buffering effect on the negative influence of life stressors on health. When SOC was added, the association of self-esteem with mental health disappeared in both areas, but optimism in the urban area and humor in the rural area were directly and independently associated with mental health., Conclusions: Our findings indicate that resources available to urban and rural residents are characteristic of the area where they live, and that social and psychological resources as well as SOC are associated with better mental health. Possible directions for health support strategies, reflecting regional characteristics, are suggested.

This study on individuals with type 2 diabetes living in Japan aimed to examine work-related factors that influence self-care and psychological health among people. A cross-sectional survey was conducted among 121 working adults with type 2 diabetes. A self-report questionnaire assessed demographics, work characteristics, self-disclosure of diabetes, support in the workplace, work-related difficulties due to diabetes, and workplace conformity. Dietary self-care, exercise, depression, and emotional distress were also evaluated. The results indicated statistically significant influence of working night shifts, self-disclosure of diabetes, and workplace conformity on dietary self-care. Work-related difficulties due to diabetes had negative effects on depression and emotional distress, and job control and support in the workplace were found to be correlated with emotional distress. These findings suggest that work-related factors have an impact on some forms of self-care activities and psychological health and that it is important to increase understanding of these issues and provide appropriate support for workers through education and counseling and adjustments in the workplace., (© 2012 Wiley Publishing Asia Pty Ltd.)

Aims: The objectives of this study were to understand the experiences of people with cleft lip and cleft palate (CLCP) and to describe the processes and factors leading to the acquisition of high self-esteem., Methods: Semi-structured interviews were conducted of 19 subjects with CLCP recruited via hospitals and through snowball sampling, and the results were analyzed qualitatively, comparing high and low self-esteem groups., Results: Participants with high self-esteem had gone through the phases of "noticing their difference from others", "knowing about and deepening their understanding of CLCP", "no denial of their life with CLCP" and "affirmation of life with CLCP". Seven factor categories including "received sufficient explanation of CLCP condition (from parents) in the early stage", "have not received negative messages about CLCP" and "feeling the presence of someone who accepts their feelings and supports them" were extracted as factors promoting these processes., Conclusions: Knowing about and understanding CLCP enables individuals to acquire a sense of coherence in their lives, which may be related to gaining a feeling of control over their cleft condition, acquiring a sense of autonomy, and finding a meaning for their lives. Thus, medical professionals should provide explanations that enable patients to understand CLCP, and also facilitate interaction between patients with the same condition., (© 2011 The Authors. Japan Journal of Nursing Science © 2011 Japan Academy of Nursing Science.)

When we look at a stationary object, the perceived direction of gaze (where we are looking) is aligned with the physical direction of eyes (where our eyes are oriented) by which the object is foveated. However, this alignment may not hold in a dynamic situation. Our experiments assessed the perceived locations of two brief stimuli (1 ms) simultaneously displayed at two different physical locations during a saccade. The first stimulus was in the instantaneous location to which the eyes were oriented and the second one was always in the same location as the initial fixation point. When the timing of these stimuli was changed intra-saccadically, their perceived locations were dissociated. The first stimuli were consistently perceived near the target that will be foveated at saccade termination. The second stimuli once perceived near the target location, shifted in the direction opposite to that of saccades, as its latency from saccades increased. These results suggested an independent adjustment of gaze orientation from the physical orientation of eyes during saccades. The spatial dissociation of two stimuli may reflect sensorimotor control of gaze during saccades.

Children in early adolescence and their mothers were studied to clarify the association between a child's sense of coherence (SOC) and its mother's SOC, the quality of family relationships as gauged by the mother, and the child's positive life experiences at home. An anonymous self-administered group questionnaire was given to all 1540 students of a high school in Tokyo, and a similar questionnaire was sent by mail to their legal guardians. Responses were received from 1505 students (response rate: 97.7%) and 989 legal guardians (response rate: 64.2%); questionnaires completed by legal guardians who were the mothers of the students were paired with the corresponding child's questionnaire. The SOC scores of mothers and students were calculated, and hierarchical multiple regression analysis was performed with the student's SOC as a dependent variable. Results for boys revealed that a mother's SOC was directly related to the child's SOC, regardless of family relationships and participation in decision-making at home. For girls, a mother's SOC was related to family relationships and was indirectly related to the child's SOC through the child's participation in decision-making at home. Results revealed that for both boys and girls, a mother's SOC had an effect on the child's SOC, and this corroborates the hypothesis of Antonovsky.

We investigated the role of inositol 1, 4, 5-trisphosphate receptors (IP3Rs), activated during preconditioning low-frequency afferent stimulation (LFS), in the subsequent induction of long-term potentiation (LTP) in CA3 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential (EPSP) by the delivery of high-frequency stimulation (HFS, a tetanus of two trains of 100 pulses at 100Hz with a 10s interval) to mossy fiber-CA3 neuron synapses was suppressed when CA3 synapses were preconditioned by the LFS of 1000 pulses at 2Hz and this effect was inhibited when the LFS preconditioning was performed in the presence of an IP3R antagonist or a protein phosphatase inhibitor. Furthermore, activation of group 1 metabotropic glutamate receptors (mGluRs) during HFS canceled the effects of an IP3R antagonist given during preconditioning LFS on the subsequent LTP induction at mossy fiber-CA3 synapses. These results suggest that, in hippocampal mossy fiber-CA3 neuron synapses, activation of IP3Rs during a preconditioning LFS results in dephosphorylation events that lead to failure of the HFS to induce subsequent LTP., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Diacylglycerol kinase (DGK) plays a key role in pathophysiological cellular responses by regulating the levels of a lipid messenger diacylglycerol. Of DGK isozymes, DGKζ localizes to the nucleus in various cells such as neurons. We previously reported that DGKζ translocates from the nucleus to the cytoplasm in hippocampal CA1 pyramidal neurons after 20 min of transient forebrain ischemia. In this study, we examined the underlying mechanism of DGKζ translocation using hippocampal slices exposed to oxygen-glucose deprivation (OGD) to simulate an ischemic model of the brain. DGKζ-immunoreactivity gradually changed from the nucleus to the cytoplasm in CA1 pyramidal neurons after 20 min of OGD and was never detected in the nucleus after reoxygenation. Intriguingly, DGKζ was detected in the nucleus at 10 min OGD whereas the following 60 min reoxygenation induced complete cytoplasmic translocation of DGKζ. Morphometric analysis revealed that DGKζ cytoplasmic translocation correlated with nuclear shrinkage indicative of an early process of neuronal degeneration. The translocation under OGD conditions was blocked by NMDA receptor (NMDAR) inhibitor, and was induced by activation of NMDAR. Chelation of the extracellular Ca(2+) blocked the translocation under OGD conditions. These results show that DGKζ cytoplasmic translocation is triggered by activation of NMDAR with subsequent extracellular Ca(2+) influx. Furthermore, inhibition of PKC activity under OGD conditions led to nuclear retention of DGKζ in about one-third of the neurons, suggesting that PKC activity partially regulates DGKζ cytoplasmic translocation. These findings provide clues to guide further investigation of glutamate excitotoxicity mechanisms in hippocampal neurons.

The aim of this study was to use longitudinal data and investigate by sex the following four hypotheses on the relationship between sense of coherence (SOC) and work environment (WE): (i) a bidirectional cause-effect relationship exists; (ii) WE is the cause and SOC is the effect; (iii) SOC is the cause and WE is the effect; and (iv) no cause-effect relationship exists. Male and female subjects between the ages of 20 and 40 living in Japan were selected as subjects by two-stage stratified random sampling, and self-administered questionnaires were sent by mail between January and March 2007 (Time 1). A follow-up was conducted in the same way from January to March of 2008 (Time 2). Responses were obtained from 3,965 individuals (follow-up ratio: 82.6%). This study analyzed 1,291 males and 933 females who were at least 25 years old at Time 1 and who worked the same job in both time periods. The analysis was performed using a cross-lagged model under structural equation modeling. The second hypothesis was selected for both males and females based on the outcome of nested model comparisons. That is, a temporal cause-effect relationship was observed between SOC and WE for both males and females, with WE as the cause and SOC as the effect.

Gangliosides (sialic acid-containing glycosphingolipids) play important roles in many physiological functions, including synaptic plasticity in the hippocampus, which has been suggested as the basal cellular process of learning and memory in the brain. In the present study, long-term potentiation (LTP) and long-term depression (LTD) in CA1 hippocampal neurons and learning behavior were examined in mice treated with (D)-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol ((D)-PDMP), an inhibitor of ganglioside biosynthesis. Mice treated with (D)-PDMP, but not those treated with (L)-PDMP, showed impairment of LTP induction in hippocampal CA1 neurons without any significant change in LTD formation and also showed a failure of learning in the 4-pellet taking test. These results indicate that de novo synthesis of gangliosides in the brain is involved in synaptic plasticity of LTP in mouse hippocampal CA1 neurons and plays important roles in learning and memory.

Background: Web 2.0 has improved interactions among peers on the Internet, especially for the many online patient communities that have emerged over the past decades. Online communities are said to be particularly beneficial peer support resources for patients with breast cancer. However, most studies of online patient communities have focused on those members who post actively (posters), even though there are many members who participate without posting (lurkers). In addition, little attention has been paid to the usage of online communities among non-English-speaking patients., Objective: The present study explored the differences in peer support received by lurkers and posters in online breast cancer communities. It also examined the effects of such support on both groups' mental health., Methods: We conducted an exploratory, descriptive, cross-sectional, Web-based survey among members of four Japanese online breast cancer communities. In an online questionnaire, we asked questions regarding sociodemographics, disease-related characteristics, mental health, participation in online communities, and peer support received from those communities., Results: Of the 465 people who accessed the questionnaire, 253 completed it. Of the respondents, 113/220 (51.4%) were lurkers. There was no significant difference between lurkers and posters with regard to sociodemographic variables. About half of the posters had been given a diagnosis of breast cancer less than a year previously, which was a significantly shorter period than that of the lurkers (P = .02). The 5 support functions extracted by factor analysis were the same for both posters and lurkers. These were emotional support/helper therapy, emotional expression, conflict, advice, and insight/universality. When the support scores were calculated, insight/universality scored highest for both posters and lurkers, with scores that were not significantly different between the two groups. Among the 5 support scores, emotional support/helper therapy and emotional expression were significantly higher among posters. For posters, emotional support/helper therapy and advice were negatively correlated with the anxiety subscale of the Hospital Anxiety and Depression Scale. Emotional expression, advice, and insight/universality were negatively correlated with the anxiety subscale for lurkers., Conclusion: We found that posters felt they received more benefits from online communities than lurkers did, including emotional support, helping other patients, and expressing their emotions. Yet even lurkers were found to gain a certain amount of peer support through online communities, especially with regard to advice and insight/universality. The results demonstrate that participation in online communities--even as a lurker--may be beneficial to breast cancer patients' mental health.

Objectives: This study sought to clarify changes in both Sense of Coherence (SOC) and social support during one year and causal relationships among upper-grade elementary school children., Methods: A one-year longitudinal survey using a self-rating questionnaire containing measures regarding individual attributes, SOC, and social support was conducted for all 403 pupils from 4th to 6th grade at a public elementary school in a suburban area of Kanagawa prefecture. Latent growth curve analysis was carried out on 237 pupils who completed all three surveys, conducted once in each semester. Firstly, to observe both overall and individual changes in SOC and social support scores, a model was constructed for each score, using the score for each semester as an observable variable, intercept (signifying the score of the first semester) and slope (signifying change of score during a year) as latent variables, and grade and sex as independent variables. Then, models of both were combined to examine causal relationships., Results: For change in SOC score, the mean slope was 0.01 (n.s.) with a variance of 2.85 (P<.05). Thus the score had no change overall, but there were pupils whose scores gradually rose or fell during the year. For change in social support score, the mean slope was -1.25 (P<.05) and its variance was 8.47 (P<.01). Therefore, the score showed an overall decrease, but there were pupils whose scores gradually rose. Grade and sex were not related to change in either score. The intercept of the social support score contributed to the slope of the SOC score (0.44, P<.001), and the intercept of the SOC score contributed to the slope of the social support score (0.34 P<0.05). Thus, a high score of social support in the first semester raised the SOC scores in the following second and third semesters, and a high score of SOC in the first semester raised subsequent social support scores. Grade and sex were not related to these associations., Conclusion: Among 237 upper-grade elementary school children, it was found that SOC overall demonstrated no change and social support decreased over one year. Pupils whose social support was abundant in the first semester had heightened SOC subsequently, and high levels of SOC in the first semester increased social support thereafter. Therefore, it was suggested that an interactive causal relationship between SOC and social support could be demonstrated by latent growth curve analysis.