SLITRK1-mediated noradrenergic projection suppression in the neonatal prefrontal cortex

SLITRK1 is an obsessive-compulsive disorder spectrum-disorders-ssociated gene that encodes a neuronal transmembrane protein. Here we show that SLITRK1 suppresses noradrenergic projections in the neonatal prefrontal cortex, and SLITRK1 functions are impaired by SLITRK1 mutations in patients with schizophrenia (S330A, a revertant of Homo sapiensspecific residue) and bipolar disorder (A444S). Slitrk1-KO newborns exhibit abnormal vocalizations, and their prefrontal cortices show excessive noradrenergic neurites and reduced Semaphorin3A expression, which suppresses noradrenergic neurite outgrowth in vitro. Slitrk1 can bind Dynamin1 and L1 family proteins (Neurofascin and L1CAM), as well as suppress Semaphorin3A-induced endocytosis. Neurofascin-binding kinetics is altered in S330A and A444S mutations. Consistent with the increased obsessive-compulsive disorder prevalence in males in childhood, the prefrontal cortex of male Slitrk1-KO newborns show increased noradrenaline levels, and serotonergic varicosity size. This study further elucidates the role of noradrenaline in controlling the development of the obsessive-compulsive disorder-related neural circuit

急性期医療を受ける患者の願い

目的：患者の地域での暮らしの希望と療養上の目標を中心に構造化した看護のプロセス”Nursing Care for Patient Goals”（NCPG）に患者の視点から示唆を得るため急性期医療を受ける患者が看護師に知ってほしい情報と療養の目標に対して求める看護を明らかにした． 方法：１特定機能病院において入院中または入院予定の20歳以上の患者を対象として質問紙調査を２回（2017年，2018年）に実施した．調査内容は基本属性，調査Ⅰ（2017年）は先行研究を基に抽出した患者情報23項目について看護師に知って欲しいと思う程度，最も大事と思う項目とその選択理由，調査Ⅱ（2018年）は自分の療養の目標について求める看護であった．統計分析は記述統計，因子分析，t 検定を用いた．自由記述によるデータは質的記述的分析を行った． 結果：調査Ⅰの有効回答数は448名で，看護師に知ってほしい自分の情報として【第１因子：社会的役割と環境】【第２因子：病気の理解・受け入れと心理】【第３因子：身体的状態と生活の仕方】【第４因子：暮らしの希望と自己決定】が抽出された．65歳未満と比較して65歳以上の対象者は第１因子が高い傾向にあった．また第４因子を最も大事と思う項目の選択理由について， “希望・目標がなきゃ生きていけない” という表現が特徴として出された．調査Ⅱの有効回答数は416名で，多数の対象者が自分の目標を医療者と共有することが重要だと感じており，受けたい看護として，傍にいて寄り添う看護，治療・症状への専門的な看護，地域での暮らしの自立への看護が抽出された． 結論：患者の視点から看護師に知ってほしい情報として４つの因子と自分の目標を分ってほしいとする対象者の願いは，希望と目標を基盤としたNCPG の考え方と一致しており，目標達成のために受けたい看護の３つの視点が示唆された．Objective : This study aimed to identify information on care of patients receiving acute care for life in community from the patientsʼ perspective and to obtain suggestions for “Nursing Care for Patient Goals”（NCPG）. Method : The subjects were patients receiving acute care and aged 20 years and above. They were given self-administered questionnaires. Survey Ⅰ（2017）consisted of a questionnaire that was based on previously collected qualitative data and comprised 23 Likert-scale questions and free descriptive questions on the reasons for selecting the most important item. Survey Ⅱ（2018）consisted of questionnaire that was comprised of three Likert-scale questions on goals and a free descriptive question on care for the achievement of goals. Statistical analysis included descriptive statistics, factor analysis, and t-test. Data from free-text descriptions were analyzed using qualitative descriptive analysis. Results : Survey Ⅰ : data from 448 valid responses were subjected to factor analysis to determine the factor structure. The following factors were identified from the patientsʼ perspectives: 1） social role and environment, 2） understanding/acceptance and psychological state, 3） physical condition and life, and 4） hope and decision-making for life. In addition, a qualitative and inductive approach was employed to analyze participantsʼ descriptive responses about the reason for selecting the most important item. The characteristic description of why participants selected “hope and decision-making of life” was “I cannot live without hope.” Survey Ⅱ : data from 416 valid responses were analyzed. The majority of participants felt it was important to share their goals with their healthcare professionals. A qualitative and inductive approach was employed to analyze the participantsʼ descriptive responses to care for goals achievement. The care desired by participants was categorized as “being with”, “professional care”, and “self-care support”. Conclusion : The factors that patients wanted nurses to know were consistent with the components of “NCPG.” The care that patients desire to achieve their goals was clarified

患者の希望を地域につなぐための患者状態とニーズ

目的：急性期医療を受ける患者の地域での生活を視野に入れた看護を展開するために患者の情報と看護の視点について明らかにすることを目的とした． 方法：特定機能病院に勤務する中堅以上の看護師３３名を対象に，地域での生活を視野に入れた患者の情報と看護の視点についてフォーカス・グループ・インタビューを行い分析した． 結果及び考察：急性期医療を受ける患者の地域での生活に必要な情報と看護の視点として，コアカテゴリー《地域での生活を可能にするニーズ》が抽出された．さらに地域での生活を可能にするための状態とニーズとして【身体・生理的な状態とニーズ】，【生活の自立と安全の状態とニーズ】，【病気の受け入れと心理的反応の状態とニーズ】，【社会的環境の状態とニーズ】，【医療・療養への自己決定の状態とニーズ】の５つのカテゴリーに分類された．これらより，患者の暮らしの希望，療養の目標，５つの視点の状態からニーズを導き看護を展開する看護の過程として，“Nursing Care for Patient Goals（” NCPG）を構造化した． 結論：地域包括ケアシステムの中において急性期医療を受ける患者の情報と看護の視点として地域での生活を可能にするための５つの状態とそのニーズが重視されていた．Objective : The aim of this study was to identify information and care perspectives of nurses for patients leaving an acute care hospital for life in the community, and to consider appropriate nursing care in the community-based integrated care system. Method : Focus group interviews were conducted with 33 nurses working in an acute care hospital. The data were analyzed using qualitative inductive analysis. Results & Discussion : The core category “Needs to enable patients to live in the community” was extracted as the information and care perspective necessary for patients receiving acute care to leave hospital for life in the community. The information and care perspectives were classified into five conditions : physical/physiological condition and needs, life independence and safety status and needs, acceptance of/emotions about illness and needs, social environment and needs, and decision-making and needs. “Nursing Care for Patient Goals” was structured as a nursing process. Conclusion : We identified five conditions and their needs that would enable patients receiving acute care to leave hospital for life in the community

Signal-transducing adaptor protein-2 has a nonredundant role for IL-33-triggered mast cell activation

Signal-transducing adaptor protein (STAP)-2 is one of the STAP family adaptor proteins and ubiquitously expressed in a variety types of cells. Although STAP-2 is required for modification of Fc epsilon RI signal transduction in mast cells, other involvement of STAP-2 in mast cell functions is unknown, yet. In the present study, we mainly investigated functional roles of STAP-2 in IL-33-induced mast cell activation. In STAP-2-deficient, but not STAP-1-deficient, mast cells, IL-33-induced IL-6 and TNF-alpha production was significantly decreased compared with that of wild-type mast cells. In addition, STAP-2-deficiency greatly reduced TLR4-mediated mast cell activation and cytokine production. For the mechanisms, STAP-2 directly binds to IKK alpha after IL-33 stimulation, leading to elevated NF-kappa B activity. In conclusion, STAP-2, but not STAP-1, participates in IL-33-induced mast cells activation

Upregulation of the dorsal raphe nucleus-prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar-Kyoto rats

<p>Wistar-Kyoto (WKY) rats are sensitive to chronic stressors and exhibit depression-like behavior. Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons projecting to the prefrontal cortex (PFC) comprise the important neurocircuitry underlying the pathophysiology of depression. To evaluate the DRN-PFC 5-HT system in WKY rats, we examined the effects of escitalopram (ESCIT) on the extracellular 5-HT level in comparison with Wistar rats using dual-probe microdialysis. The basal levels of 5-HT in the DRN, but not in the PFC, in WKY rats was reduced as low as 30% of Wistar rats. Responses of 5-HT in the DRN and PFC to ESCIT administered systemically and locally were attenuated in WRY rats. Feedback inhibition of DRN 5-HT release induced by ESCIT into the PFC was also attenuated in WKY rats. Chronic ESCIT induced upregulation of the DRN-PFC 5-HT system in WRY rats, with increases in basal 5-HT in the DRN, responsiveness to ESCIT in the DRN and PFC, and feedback inhibition, whereas downregulation of these effects was induced in Wistar rats. Thus, the WRY rat is an animal model of depression with low activity of the DRN-PFC 5HT system. The finding that chronic ESCIT upregulates the 5-HT system in hyposerotonergic WRY rats may contribute to improved understanding of mechanisms of action of antidepressants, especially in depression with 5-HT deficiency. (C) 2013 Elsevier Ltd. All rights reserved.</p>

Obligatory roles of dopamine D1 receptors in the dentate gyrus in antidepressant action of a selective serotonin reuptake inhibitor, fluoxetine

Depression is a leading cause of disability. Current pharmacological treatment of depression is insufficient, and development of improved treatments especially for treatment-resistant depression is desired. Understanding the neurobiology of antidepressant actions may lead to development of improved therapeutic approaches. Here, we demonstrate that dopamine D1 receptors in the dentate gyrus act as a pivotal mediator of antidepressant actions in mice. Chronic administration of a selective serotonin reuptake inhibitor (SSRI), fluoxetine, increases D1 receptor expression in mature granule cells in the dentate gyrus. The increased D1 receptor signaling, in turn, contributes to the actions of chronic fluoxetine treatment, such as suppression of acute stress-evoked serotonin release, stimulation of adult neurogenesis and behavioral improvement. Importantly, under severely stressed conditions, chronic administration of a D1 receptor agonist in conjunction with fluoxetine restores the efficacy of fluoxetine actions on D1 receptor expression and behavioral responses. Thus, our results suggest that stimulation of D1 receptors in the dentate gyrus is a potential adjunctive approach to improve therapeutic efficacy of SSRI antidepressants. © 2018, The Author(s).1