Journal of pharmacological sciences最新文献_第2页

Effect of antidepressants and social defeat stress on the activity of dorsal raphe serotonin neurons in free-moving animals 抗抑郁药和社交失败压力对自由活动动物中叶背血清素神经元活动的影响。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-02-01 DOI: 10.1016/j.jphs.2025.01.001

Masashi Koda , Hiroyuki Kawai , Hisashi Shirakawa , Shuji Kaneko , Kazuki Nagayasu

{"title":"Effect of antidepressants and social defeat stress on the activity of dorsal raphe serotonin neurons in free-moving animals","authors":"Masashi Koda , Hiroyuki Kawai , Hisashi Shirakawa , Shuji Kaneko , Kazuki Nagayasu","doi":"10.1016/j.jphs.2025.01.001","DOIUrl":"10.1016/j.jphs.2025.01.001","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is among the most common mental disorders worldwide and is characterized by dysregulated reward processing associated with anhedonia. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for MDD; however, their onset of action is delayed. Recent reports have shown that serotonin neurons in the dorsal raphe nucleus (DRN) are activated by rewards and play a vital role in reward processing. However, whether antidepressant treatment affects the DRN serotonin neuronal response to rewards in awake animals remains unknown. In this study, we measured the activity of DRN serotonin neurons in awake mice and determined the effects of antidepressants and chronic stress on DRN serotonin neuronal activity. We found that acute treatment with citalopram, an SSRI, significantly decreased sucrose-induced activation of DRN serotonin neurons. The decrease in response to acute citalopram treatment was attenuated by chronic citalopram treatment. Acute treatment with (<em>S</em>)-WAY100135, a 5-HT<sub>1A</sub> receptor antagonist, dose-dependently inhibited the response to acute citalopram treatment. These results indicate that autoinhibition by activating 5-HT<sub>1A</sub> receptors via acute SSRI treatment may blunt the reward response, which can be recovered after chronic SSRI treatment.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 2","pages":"Pages 113-123"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting enteric glial CRF-R1/Cx43 attenuates stress-induced accelerated colonic motility

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-27 DOI: 10.1016/j.jphs.2025.01.009

Haiqing Chang , Haifeng Zhang , Shiqiu Jiang , Juan Hu , Hongli Ma , Bo Cheng , Qiang Wang , Yansong Li

{"title":"Targeting enteric glial CRF-R1/Cx43 attenuates stress-induced accelerated colonic motility","authors":"Haiqing Chang , Haifeng Zhang , Shiqiu Jiang , Juan Hu , Hongli Ma , Bo Cheng , Qiang Wang , Yansong Li","doi":"10.1016/j.jphs.2025.01.009","DOIUrl":"10.1016/j.jphs.2025.01.009","url":null,"abstract":"<div><div>Stress triggers disorders in accelerated peristalsis, with corticotropin releasing factor receptor 1 (CRF-R1) playing a pivotal role. Enteric glia cells (EGCs) and glial Cx43 are known to influence gastrointestinal motility, yet their involvement in colonic motor responses to stress remains unclear. Using immunofluorescence and single-cell RNA sequencing data, we identified CRF-R1 expression in EGCs. Male C57BL/6 mice subjected to wrap restraint stress (WRS) revealed stress-induced colonic motility changes. By employing Fluoroacetate, NBI 27914, and Gap26, we elucidated the impact of glial CRF-R1/Cx43 on stress-induced colonic motor responses. Our study demonstrated CRF-R1 expression in EGCs of the small intestine and colon, along with elevated CRF levels and upregulated CRF-R1 in the distal colon under stress. Antagonizing CRF-R1 and disrupting EGC function made mice resistant to colonic stress responses. Mechanistically, increased glial Cx43 expression and activity influenced colonic motor responses in a CRF-R1-dependent manner. Our findings highlight the role of EGC-derived CRF-R1 in stress-induced colonic motor responses via Cx43 activation. Targeting CRF-R1/Cx43 signaling in EGCs may offer a promising approach to mitigate stress-induced colonic transit changes.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 167-178"},"PeriodicalIF":3.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of fecal microbiota transplantation on behavioral abnormality in attention deficit hyperactivity disorder-like model rats

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-27 DOI: 10.1016/j.jphs.2025.01.007

Wakana Harigai , Kanata Mikami , Mohammed E. Choudhury , Hiroto Yamauchi , Chisato Yajima , Shin Shimizu , Noriyuki Miyaue , Masahiro Nagai , Madoka Kubo , Junya Tanaka , Taiichi Katayama

{"title":"Effects of fecal microbiota transplantation on behavioral abnormality in attention deficit hyperactivity disorder-like model rats","authors":"Wakana Harigai , Kanata Mikami , Mohammed E. Choudhury , Hiroto Yamauchi , Chisato Yajima , Shin Shimizu , Noriyuki Miyaue , Masahiro Nagai , Madoka Kubo , Junya Tanaka , Taiichi Katayama","doi":"10.1016/j.jphs.2025.01.007","DOIUrl":"10.1016/j.jphs.2025.01.007","url":null,"abstract":"<div><div>Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. ADHD symptoms not only impact patients and their families but also impose societal costs. Current treatments for ADHD, including environmental adjustments and medication, are symptomatic and require long-term management. Recently, the link between gut microbiota dysbiosis and various psychiatric and neurological disorders has become evident. The effectiveness of fecal microbiota transplantation (FMT) from healthy individuals in treating autism spectrum disorder, a neurodevelopmental disorder related to ADHD, has been demonstrated. However, despite suggestions of a relationship between ADHD and gut microbiota, few studies have explored the efficacy of FMT for ADHD. In the current study, we used 16S rDNA analysis to show that ADHD-like model rats possess a gut microbiota that is distinct from that of healthy rats, and we demonstrated that FMT from healthy rats improved hyperactivity in ADHD-like model rats. Our findings suggest that differences in gut microbiota underlie ADHD-like behaviors and that FMT may be an effective treatment for ADHD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 189-198"},"PeriodicalIF":3.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Asperuloside suppresses the progression of depression through O-GlcNAcylation of IκBα and regulating NFκB signaling

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-24 DOI: 10.1016/j.jphs.2025.01.010

Li Yin , Huakun Wang , Hong Xu , Haixiao Lu , Jiayu Lv , Chengshu Lu

{"title":"Asperuloside suppresses the progression of depression through O-GlcNAcylation of IκBα and regulating NFκB signaling","authors":"Li Yin , Huakun Wang , Hong Xu , Haixiao Lu , Jiayu Lv , Chengshu Lu","doi":"10.1016/j.jphs.2025.01.010","DOIUrl":"10.1016/j.jphs.2025.01.010","url":null,"abstract":"<div><div>Depression is a pervasive mental disorder that poses a significant threat to human health globally. Asperuloside (ASP), an iridoid glycoside extracted from Herba Paederiae, exhibits a range of pharmacological activities, including anti-tumor and anti-inflammatory effects. This study aims to explore the function and molecular mechanisms of ASP in alleviating depression. Chronic unpredictable mild stress (CUMS) was employed to establish a rat model of depression. Behavioral tests were conducted to evaluate the antidepressant effects of ASP. Apoptosis in hippocampal tissues was assessed using TUNEL assay. Primary hippocampal neuron apoptosis was assessed using Annexin V/PI staining and flow cytometry, while cell death was detected via PI staining. The expression levels of target mRNAs and proteins were analyzed by quantitative PCR (qPCR) and western blotting, respectively. Additionally, the levels of O-GlcNAcylation and ubiquitination were determined by western blot analysis following immunoprecipitation. Molecular docking was performed to elucidate the interaction mode between ASP and its target protein, O-linked β-N-acetylglucosamine transferase (OGT). Our findings revealed that ASP treatment significantly ameliorated depression-like behaviors and cognitive dysfunction, as well as inhibited hippocampus apoptosis in CUMS-induced rats, Moreover, ASP inhibited LPS-induced neuronal cell apoptosis and suppressed the activation of the NF-κB signaling pathway. Mechanistically, we demonstrated that ASP promoted O-GlcNAcylation of IκBα, and suppressed its ubiquitination and phosphorylation, thereby stabilizing IκBα protein. In conclusion, ASP exerts antidepressant effects by enhancing IκBα O-GlcNAcylation, thus inhibiting its ubiquitination and phosphorylation. These findings provide a novel therapeutic target for the treatment of depression.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 179-188"},"PeriodicalIF":3.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antidepressant effect of globin digest through enhanced hippocampal neurogenesis in a mouse model of lipopolysaccharide-induced depression

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-23 DOI: 10.1016/j.jphs.2025.01.008

Osamu Nakagawasai , Kotaro Yamada , Kohei Takahashi , Fuka Niinuma , Wataru Nemoto , Koichi Tan-No

引用次数: 0

Alteration of COX-1 and TLR4 expression in the mouse brain during chronic social defeat stress revealed by Positron Emission Tomography study

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-16 DOI: 10.1016/j.jphs.2025.01.006

Yumika Motooka , Ryota Shinohara , Shiho Kitaoka , Ai Uryu , Dongrui Li , Hiroyuki Neyama , Yilong Cui , Tatsuya Kida , Wakiko Arakaki , Hisashi Doi , Yasuyoshi Watanabe , Tomoyuki Furuyashiki

{"title":"Alteration of COX-1 and TLR4 expression in the mouse brain during chronic social defeat stress revealed by Positron Emission Tomography study","authors":"Yumika Motooka , Ryota Shinohara , Shiho Kitaoka , Ai Uryu , Dongrui Li , Hiroyuki Neyama , Yilong Cui , Tatsuya Kida , Wakiko Arakaki , Hisashi Doi , Yasuyoshi Watanabe , Tomoyuki Furuyashiki","doi":"10.1016/j.jphs.2025.01.006","DOIUrl":"10.1016/j.jphs.2025.01.006","url":null,"abstract":"<div><div>Despite the recognized roles of neuroinflammation in mental illnesses, PET imaging on currently available biomarkers has limitations due to the lack of evidence demonstrating their relationship to the molecular and cellular events of inflammation associated with the pathology of mental illness. Rodent stress models, such as chronic social defeat stress (SDS), have identified crucial roles for COX-1 and TLR4, which are innate immune molecules, in chronic SDS-induced neuroinflammation and its behavioral consequences. In this study, we performed COX-1 and TLR4 PET imaging at multiple time points during chronic SDS in mice. For COX-1 PET imaging, we used the COX-1 PET probe <em>(S)</em>-[<sup>18</sup>F]KTP-Me. Subchronic SDS transiently increased uptake and slower washout in broad regions of the brain, including the cerebral cortex, hippocampus, striatum, and thalamus. For TLR4 PET imaging, we developed a new BBB-permeable PET probe, [<sup>11</sup>C]<strong>1</strong>, which detected LPS-induced neuroinflammation. Washout of [<sup>11</sup>C]<strong>1</strong> was facilitated in the cerebellum after subchronic and chronic SDS and in the pons-medulla after chronic SDS. Collectively, our findings suggest the potential usefulness of COX-1 and TLR4 PET imaging in visualizing and understanding time-dependent process of neuroinflammation in stress-related mental illnesses.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 156-166"},"PeriodicalIF":3.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Darbepoetin alfa enhances exercise performance in trained mice in a sex-specific manner

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-10 DOI: 10.1016/j.jphs.2025.01.005

Yoshinori Iba , Shinichi Sawada , Yukika Yamada , Hiroki Murai , Yoshiyuki Ishida , Daisuke Nakata , Keiji Terao

{"title":"Darbepoetin alfa enhances exercise performance in trained mice in a sex-specific manner","authors":"Yoshinori Iba , Shinichi Sawada , Yukika Yamada , Hiroki Murai , Yoshiyuki Ishida , Daisuke Nakata , Keiji Terao","doi":"10.1016/j.jphs.2025.01.005","DOIUrl":"10.1016/j.jphs.2025.01.005","url":null,"abstract":"<div><div>Erythropoiesis-stimulating agents (ESAs) increase hemoglobin mass and maximal oxygen uptake; however, it remains unclear whether the abuse of ESAs enhances exercise performance. Therefore, we herein investigated the effects of darbepoetin alfa (DPO), a long-acting erythropoietin analog, on exercise performance in trained male and female mice. Exercise performance was assessed as the number of arrivals at the halfway line of a flow rate-adjustable swimming pool. The DPO treatment significantly increased hematocrit levels regardless of sex, but only enhanced exercise performance in female mice. The sex-specific effect of DPO on exercise performance was not abolished by ovariectomy; the enhancing effect was more pronounced in ovariectomized (OVX) mice than in female mice. This effect of the DPO treatment was attributed to a significant increase in the gene expression of PGC-1alpha in the gastrocnemius (GASTR) muscle of OVX mice, but not female mice. In addition, myocyte hypertrophy, but not angiogenesis, was observed in the GASTR muscle of DPO-treated OVX mice. These results revealed the sex-specific enhancing effect of DPO on exercise performance in trained mice. Enhanced exercise performance did not appear to require female sex hormones and may not be due to direct effects on skeletal muscles.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 131-138"},"PeriodicalIF":3.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CCN1 derived from vascular endothelial cells impairs cognitive function in Alzheimer’s disease model mice

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-09 DOI: 10.1016/j.jphs.2025.01.004

Shuntaro Hirabayashi , Akiko Uyeda , Ichiro Manabe , Yoshino Yonezu , Takashi Saito , Takaomi C. Saido , Hidemi Misawa , Yuki Ogasawara , Kaoru Kinoshita , Rieko Muramatsu

{"title":"CCN1 derived from vascular endothelial cells impairs cognitive function in Alzheimer’s disease model mice","authors":"Shuntaro Hirabayashi , Akiko Uyeda , Ichiro Manabe , Yoshino Yonezu , Takashi Saito , Takaomi C. Saido , Hidemi Misawa , Yuki Ogasawara , Kaoru Kinoshita , Rieko Muramatsu","doi":"10.1016/j.jphs.2025.01.004","DOIUrl":"10.1016/j.jphs.2025.01.004","url":null,"abstract":"<div><div>Vascular endothelial cell-expressing molecules regulate neuronal function. Although cerebrovascular dysregulation is a hallmark of Alzheimer’s disease (AD), the effect of changes in molecular expression on neuronal function in vascular endothelial cells during disease progression is not clear. In this study, we demonstrated that the cellular communication network factor 1 (CCN1), which is highly expressed in vascular endothelial cells during the chronic stage of AD in mice, is involved in the impairment of cognitive function. Vascular endothelial cells isolated from the brains of <em>App</em><sup><em>NL-G-F</em></sup> mice show differential expression of genes, including CCN1. CCN1 treatment decreased the synaptic number in cultured hippocampal cells, with changes in the expression of genes associated with morphological changes. <em>In vivo</em>, <em>App</em><sup><em>NL-G-F</em></sup> mice with CCN1 silencing in vascular endothelial cells demonstrated high spine density and improved spatial learning. No significant change was observed in the number of microglia/macrophages, astrocytes, and amyloid-beta (Aβ) accumulation in the hippocampus of the mice. These results suggest that CCN1 is a key factor modulating neurological dysfunction through neurovascular interactions.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 3","pages":"Pages 146-155"},"PeriodicalIF":3.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Minocycline prevents monocrotaline-induced pulmonary hypertension through the attenuation of endothelial dysfunction and vascular wall thickening 二甲胺四环素通过抑制内皮功能障碍和血管壁增厚来预防单罗他林诱导的肺动脉高压。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-01 DOI: 10.1016/j.jphs.2024.12.002

Ryo Niijima , Kosuke Otani , Tomoko Kodama , Muneyoshi Okada , Hideyuki Yamawaki

{"title":"Minocycline prevents monocrotaline-induced pulmonary hypertension through the attenuation of endothelial dysfunction and vascular wall thickening","authors":"Ryo Niijima , Kosuke Otani , Tomoko Kodama , Muneyoshi Okada , Hideyuki Yamawaki","doi":"10.1016/j.jphs.2024.12.002","DOIUrl":"10.1016/j.jphs.2024.12.002","url":null,"abstract":"<div><div>Pulmonary hypertension (PH) is a progressive disease with a poor prognosis in which high pulmonary artery pressure leads to right heart failure, therefore, there is an urgent need to elucidate pathological mechanisms and to develop new treatment for PH. Minocycline has not only antibacterial effects but also anti-inflammatory effects in various tissues. We hypothesize that minocycline could prevent PH development in rats. PH was induced by a single intraperitoneal injection of monocrotaline (MCT, 60 mg/kg), and minocycline (20 mg/kg) was treated daily for 14 days from the day of MCT injection. Minocycline inhibited the rise in mean pulmonary arterial pressure of MCT-induced PH rats and improved the attenuation of acetylcholine-induced relaxation in isolated intrapulmonary artery from MCT-induced PH rats. Minocycline further inhibited vascular wall thickening of pulmonary arterioles and showed a tendency to inhibit the muscularization of pulmonary arterioles in MCT-induced PH rats. PH-preventing effect of minocycline does not seem to be mediated via the actions on matrix metalloproteinase, inflammatory cytokines, and mast cells migration in lung. In summary, we revealed for the first time that minocycline ameliorated the MCT-induced PH in rats, at least partly through preventing pulmonary artery endothelial dysfunction and wall thickening.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 1","pages":"Pages 39-44"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transient receptor potential vanilloid 4 gene-deficiency attenuates the inhibitory effect of 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid on vascular permeability in mice 瞬时受体电位香草酸4基因缺失可减弱5,6-二羟基- 8z、11Z、14Z、17z -二十碳四烯酸对小鼠血管通透性的抑制作用。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-01-01 DOI: 10.1016/j.jphs.2024.11.005

Kotoha Inoue , Shinya Takenouchi , Misato Kida , Makiko Kashio , Makoto Tominaga , Takahisa Murata

引用次数: 0