Fundamental & Clinical Pharmacology最新文献

{"title":"Differential Effects of Prenatal Poly I:C Exposure and Antipsychotics on NMDA/GABA Receptors and GSK3β-Mediated Signaling in the Dorsal Raphe Nucleus of Female Rats","authors":"Shiyan Chen,&nbsp;Jiamei Lian,&nbsp;Yueqing Su,&nbsp;Chao Deng","doi":"10.1111/fcp.70033","DOIUrl":"https://doi.org/10.1111/fcp.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The dorsal raphe nucleus (DRN) is the origin of the 5-HT neurotransmission pathways. The 5-HT, dopamine D2, GABA, and NMDA receptors, as well as the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and G protein-independent protein kinase B (PKB/Akt)-glycogen synthase kinase 3β (GSK3β) signaling, are involved in the pathophysiology of schizophrenia and are modulated by antipsychotics. However, their pathological changes and antipsychotic modulations in the DRN are not well understood in schizophrenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study explored effects of antipsychotics on NMDA and GABA_A receptors, as well as PKA, AKT-GSK3β, cAMP-responsive element-binding protein 1 (CREB1), and disheveled (Dvl)-β-catenin signaling in the DRN using a maternal immune activation rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prenatal polyriboinosinic-polyribocytidylic acid (Poly I:C) exposure was delivered at gestational Day 15. Female rats were treated with risperidone, olanzapine, or vehicle from postnatal day 70 for 35 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prenatal Poly I:C exposure increased mRNA expression of NMDA receptor <i>Grin2a/2b</i> subunits, the GABA_A receptor <i>β3</i> subunit, glutamic acid decarboxylase 1 (<i>GAD1</i>), <i>AKT1/3</i>, and <i>GSK3β</i> in the DRN. Antipsychotics significantly increased the mRNA expression of <i>PKA</i>, <i>CREB1</i>, <i>β-catenin</i>, <i>GSK3β</i>, and <i>Grin2d</i> subunits in the DRN of Poly I:C rats. Prenatal Poly I:C exposure led to decreased expression of <i>GAD2</i>, which was partially reversed antipsychotics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study suggests that prenatal Poly I:C exposure and antipsychotics differentially modulate NMDA and GABA_A receptors, as well as AKT-GSK3β, PKA-CREB1, and Dvl-β-catenin signaling in the DRN of rats. Poly I:C mainly influenced the AKT-GSK3β signaling, while antipsychotics modulated the AKT-GSK3β, PKA-CREB1, and Dvl-GSK3β-β-catenin signaling pathways in the DRN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Master 2 award","authors":"","doi":"10.1111/fcp.70019","DOIUrl":"https://doi.org/10.1111/fcp.70019","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discussed poster abstracts—PM2","authors":"","doi":"10.1111/fcp.70022","DOIUrl":"https://doi.org/10.1111/fcp.70022","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug news and therapeutic news","authors":"","doi":"10.1111/fcp.70017","DOIUrl":"https://doi.org/10.1111/fcp.70017","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral communication abstracts","authors":"","doi":"10.1111/fcp.70018","DOIUrl":"https://doi.org/10.1111/fcp.70018","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thesis awards","authors":"","doi":"10.1111/fcp.70020","DOIUrl":"https://doi.org/10.1111/fcp.70020","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discussed poster abstracts—PM1","authors":"","doi":"10.1111/fcp.70021","DOIUrl":"https://doi.org/10.1111/fcp.70021","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poster abstracts","authors":"","doi":"10.1111/fcp.70023","DOIUrl":"https://doi.org/10.1111/fcp.70023","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theme and main topic index","authors":"","doi":"10.1111/fcp.70024","DOIUrl":"https://doi.org/10.1111/fcp.70024","url":null,"abstract":"","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 S1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors and Multiple Interaction Effects for Hyperammonemia in Patients Receiving Valproic Acid","authors":"Chien-Chou Su,&nbsp;Tsai-Kuei Huang,&nbsp;Ching-Sen Shih,&nbsp;Yi-Chia Su","doi":"10.1111/fcp.70030","DOIUrl":"https://doi.org/10.1111/fcp.70030","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Valproic acid (VPA) use is associated with an increased risk of hyperammonemia (HA); however, the specific interactions between HA risk factors in VPA-treated patients remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to identify and assess the effects of multiple interactions between different risk factors affecting HA to improve clinical risk stratification in patients undergoing VPA therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study by reviewing the medical records of patients treated with VPA at a single center from January 2019 to December 2021. The SHapley Additive exPlanations (SHAP) method was used to interpret model predictions, revealing the relative importance and interactions of factors affecting HA risk. SHAP interaction scores were used to assess the effects of multiple interactions between features, providing a comprehensive analysis of how risk factors interact.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study identified the Top 15 predictors of HA, ranked by importance: patient age, VPA blood concentration, VPA dose, epilepsy, VPA treatment duration, levetiracetam use, hypertension, mental disorders, and number of medications. Notable multiple interaction effects were observed, particularly between age and factors including VPA concentration, epilepsy, and treatment duration. Younger patients and those with elevated VPA concentrations were at increased risk of developing HA, especially when epilepsy or polypharmacy were present.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study highlights several critical factors potentially influencing HA development in VPA-treated patients, particularly younger patients, those with epilepsy, or those undergoing polypharmacy. However, as a single-center retrospective study, these findings necessitate further validation through additional research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"39 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}