Journal of pharmacological sciences最新文献_第6页

Laminar-selective spinal astrocyte population capable of converting tactile information into nociceptive in rats 能将大鼠触觉信息转化为痛觉信息的层状选择性脊髓星形胶质细胞群

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-27 DOI: 10.1016/j.jphs.2024.02.014

Daichi Sueto , Akihisa Onishi , Eriko I , Yu Yoshikawa , Makoto Tsuda

引用次数: 0

Icariin alleviates diabetic renal interstitial fibrosis aggravation by inhibiting miR-320a-3p targeting BMP6 淫羊藿苷通过抑制以 BMP6 为靶点的 miR-320a-3p 减轻糖尿病肾间质纤维化的恶化

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-27 DOI: 10.1016/j.jphs.2024.02.013

Kaiwei Wang , Mengjun Hou , Chen Qiao , Yalei Duan , Rongpin Tao , Xiniao Wang , Kang Xiao , Shuo Liu , Hanzhen Zhao , Jiali Wang , Zhirong Jia , Xuansheng Ding

{"title":"Icariin alleviates diabetic renal interstitial fibrosis aggravation by inhibiting miR-320a-3p targeting BMP6","authors":"Kaiwei Wang , Mengjun Hou , Chen Qiao , Yalei Duan , Rongpin Tao , Xiniao Wang , Kang Xiao , Shuo Liu , Hanzhen Zhao , Jiali Wang , Zhirong Jia , Xuansheng Ding","doi":"10.1016/j.jphs.2024.02.013","DOIUrl":"10.1016/j.jphs.2024.02.013","url":null,"abstract":"<div><p>Diabetic nephropathy is a common complication of diabetes, accumulating evidence underscores the pivotal role of tubulointerstitial fibrosis in the progression of diabetic nephropathy. However, the underlying mechanisms remain incompletely understood. Although the mechanisms in diabetic nephropathy fibrosis have been the focus of many studies, only limited information is currently available concerning microRNA regulation in tubulointerstitial fibrosis. In this study, we aimed to investigate the roles of miR-320a-3p and bone morphogenetic protein-6 (BMP6) in tubulointerstitial fibrosis. After inducing fibrosis with high glucose in HK-2 cells, we found that miR-320a-3p is significantly up-regulated, whereas BMP6 is markedly down-regulated. These changes suggest close link between miR-320a-3p and BMP6 in tubulointerstitial fibrosis. To elucidate this phenomenon, miR-320a-3p mimic, inhibitor and siBMP6 were employed. We observed in miR-320a-3p mimic group the fibrosis marker include alpha smooth muscle actin and type I collagen was significantly up-regulated, whereas BMP6 exhibited the opposite trend. Additionally, we found icariin could alleviate tubulointerstitial fibrosis by downregulation the miR-320a-3p expression. In conclusion, miR-320a-3p promotes tubulointerstitial fibrosis during the development of DN by suppressing BMP signal pathway activity via inhibiting BMP6 expression. Suggesting that miR-320a-3p represents a potential therapeutic target for tubulointerstitial fibrosis induced by diabetic nephropathy.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 316-325"},"PeriodicalIF":3.5,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000240/pdfft?md5=5fc125f051c623748311765e84eb65b5&pid=1-s2.0-S1347861324000240-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010803","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

Identification of tumor-suppressive miRNAs that target amino acid transporter LAT1 and exhibit anti-proliferative effects on cholangiocarcinoma cells 鉴定靶向氨基酸转运体 LAT1 并对胆管癌细胞具有抗增殖作用的抑癌 miRNAs

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-24 DOI: 10.1016/j.jphs.2024.02.012

Xingming Liu , Kou Nishikubo , Ryuichi Ohgaki , Hiroki Okanishi , Suguru Okuda , Minhui Xu , Yoshikatsu Kanai

{"title":"Identification of tumor-suppressive miRNAs that target amino acid transporter LAT1 and exhibit anti-proliferative effects on cholangiocarcinoma cells","authors":"Xingming Liu , Kou Nishikubo , Ryuichi Ohgaki , Hiroki Okanishi , Suguru Okuda , Minhui Xu , Yoshikatsu Kanai","doi":"10.1016/j.jphs.2024.02.012","DOIUrl":"10.1016/j.jphs.2024.02.012","url":null,"abstract":"<div><p>Amino acid transporter LAT1 is highly upregulated in various cancer types, including cholangiocarcinoma (CHOL), and contributes to the rapid proliferation of cancer cells and disease progression. However, the molecular mechanisms underlying the pathological upregulation of LAT1 remain largely unknown. This study pursued the possibility of miRNA-mediated regulation of the LAT1 expression in CHOL cells. Using online target prediction methods, we extracted five candidate miRNAs commonly predicted to regulate the LAT1 expression. Three of them, miR-194-5p, miR-122-5p, and miR-126-3p, were significantly downregulated in CHOL cancer compared to normal tissues. Correlation analysis revealed weak-to-moderate negative correlations between the expression of these miRNAs and LAT1 mRNA in CHOL cancer tissues. We selected miR-194-5p and miR-122-5p for further analyses and found that both miRNAs functionally target 3′UTR of LAT1 mRNA by a luciferase-based reporter assay. Transfection of the miRNA mimics significantly suppressed the LAT1 expression at mRNA and protein levels and inhibited the proliferation of CHOL cells, with a trend of affecting intracellular amino acids and amino acid-related signaling pathways. This study indicates that the decreased expression of these LAT1-targeting tumor-suppressive miRNAs contributes to the upregulation of LAT1 and the proliferation of CHOL cells, highlighting their potential for developing novel cancer therapeutics and diagnostics.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 301-311"},"PeriodicalIF":3.5,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000239/pdfft?md5=9adf6144f5deb4537a797a8cd08e9b83&pid=1-s2.0-S1347861324000239-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139954619","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 D-allose on ATP production and cell viability in neonatal rat cardiomyocytes D-allose 对新生大鼠心肌细胞 ATP 生成和细胞活力的影响

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-15 DOI: 10.1016/j.jphs.2024.02.009

Xi Chen , Asadur Rahman , Steeve Akumwami , Asahiro Morishita , Kento Kitada , Yasumasa Ikeda , Masafumi Funamoto , Akira Nishiyama

引用次数: 0

Chronic stress alters lipid mediator profiles associated with immune-related gene expressions and cell compositions in mouse bone marrow and spleen 慢性应激改变了小鼠骨髓和脾脏中与免疫相关基因表达和细胞组成有关的脂质介质谱系

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-15 DOI: 10.1016/j.jphs.2024.02.010

Io Horikawa , Hirotaka Nagai , Masayuki Taniguchi , Guowei Chen , Masakazu Shinohara , Tomohide Suzuki , Shinichi Ishii , Yoshio Katayama , Shiho Kitaoka , Tomoyuki Furuyashiki

{"title":"Chronic stress alters lipid mediator profiles associated with immune-related gene expressions and cell compositions in mouse bone marrow and spleen","authors":"Io Horikawa , Hirotaka Nagai , Masayuki Taniguchi , Guowei Chen , Masakazu Shinohara , Tomohide Suzuki , Shinichi Ishii , Yoshio Katayama , Shiho Kitaoka , Tomoyuki Furuyashiki","doi":"10.1016/j.jphs.2024.02.010","DOIUrl":"10.1016/j.jphs.2024.02.010","url":null,"abstract":"<div><p>Despite the importance of lipid mediators in stress and depression and their link to inflammation, the influence of stress on these mediators and their role in inflammation is not fully understood. This study used RNA-seq, LC-MS/MS, and flow cytometry analyses in a mouse model subjected to chronic social defeat stress to explore the effects of acute and chronic stress on lipid mediators, gene expression, and cell population in the bone marrow and spleen. In the bone marrow, chronic stress induced a sustained transition from lymphoid to myeloid cells, accompanied by corresponding changes in gene expression. This change was associated with decreased levels of 15-deoxy-d12,14-prostaglandin J<sub>2</sub>, a lipid mediator that inhibits inflammation. In the spleen, chronic stress also induced a lymphoid-to-myeloid transition, albeit transiently, alongside gene expression changes indicative of extramedullary hematopoiesis. These changes were linked to lower levels of 12-HEPE and resolvins, both critical for inhibiting and resolving inflammation. Our findings highlight the significant role of anti-inflammatory and pro-resolving lipid mediators in the immune responses induced by chronic stress in the bone marrow and spleen. This study paves the way for understanding how these lipid mediators contribute to the immune mechanisms of stress and depression.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 279-293"},"PeriodicalIF":3.5,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000215/pdfft?md5=d0923d053b1625bac5010259dd286bd9&pid=1-s2.0-S1347861324000215-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139833182","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

Seihaito, a Kampo medicine, attenuates IL-13-induced mucus production and goblet cell metaplasia Seihaito 是一种堪布药，可减少 IL-13 诱导的粘液分泌和上皮细胞增生

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-13 DOI: 10.1016/j.jphs.2024.02.008

Tomoki Sekiya, Kazuhito Murakami, Yoichiro Isohama

{"title":"Seihaito, a Kampo medicine, attenuates IL-13-induced mucus production and goblet cell metaplasia","authors":"Tomoki Sekiya, Kazuhito Murakami, Yoichiro Isohama","doi":"10.1016/j.jphs.2024.02.008","DOIUrl":"10.1016/j.jphs.2024.02.008","url":null,"abstract":"<div><p>Goblet cell hyperplasia and increased mucus production are features of airway diseases, including asthma, and excess airway mucus often worsens these conditions. Even steroids are not uniformly effective in mucus production in severe asthma, and new therapeutic options are needed. Seihaito is a Japanese traditional medicine that is used clinically as an antitussive and expectorant. In the present study, we examined the effect of Seihaito on goblet cell differentiation and mucus production. In <em>in vitro</em> studies, using air–liquid interface culture of guinea-pig tracheal epithelial cells, Seihaito inhibited IL-13-induced proliferation of goblet cells and MUC5AC, a major component of mucus production. Seihaito suppressed goblet cell-specific gene expression, without changing ciliary cell-specific genes, suggesting that it inhibits goblet cell differentiation. In addition, Seihaito suppressed <em>MUC5AC</em> expression in cells transfected with <em>SPDEF</em>, a transcription factor activated by IL-13. Furthermore, Seihaito attenuated <em>in vivo</em> goblet cell proliferation and <em>MUC5AC</em> mRNA expression in IL-13-treated mouse lungs. Collectively, these findings demonstrated that Seihaito has an inhibitory effect on goblet cell differentiation and mucus production, which is at least partly due to the inhibition of SPDEF.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"155 2","pages":"Pages 21-28"},"PeriodicalIF":3.5,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000197/pdfft?md5=582d82ecef1c0bf646e122f4d4b17aff&pid=1-s2.0-S1347861324000197-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139889843","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

LPS priming-induced immune tolerance mitigates LPS-stimulated microglial activation and social avoidance behaviors in mice LPS 引物诱导的免疫耐受可减轻 LPS 刺激的小鼠微胶质细胞活化和社交回避行为

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-10 DOI: 10.1016/j.jphs.2024.02.006

Vichuda Charoensaensuk , Bor-Ren Huang , Sian-Ting Huang , Chingju Lin , Sheng-Yun Xie , Chao-Wei Chen , Yen-Chang Chen , Han-Tsung Cheng , Yu-Shu Liu , Sheng-Wei Lai , Ching-Kai Shen , Hui-Jung Lin , Liang-Yo Yang , Dah-Yuu Lu

{"title":"LPS priming-induced immune tolerance mitigates LPS-stimulated microglial activation and social avoidance behaviors in mice","authors":"Vichuda Charoensaensuk , Bor-Ren Huang , Sian-Ting Huang , Chingju Lin , Sheng-Yun Xie , Chao-Wei Chen , Yen-Chang Chen , Han-Tsung Cheng , Yu-Shu Liu , Sheng-Wei Lai , Ching-Kai Shen , Hui-Jung Lin , Liang-Yo Yang , Dah-Yuu Lu","doi":"10.1016/j.jphs.2024.02.006","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.02.006","url":null,"abstract":"<div><p>In this study, we investigated the regulatory mechanisms underlying the effects of LPS tolerance on the inflammatory homeostasis of immune cells. LPS priming–induced immune tolerance downregulated cyclooxygenase-2, and lowered the production of prostaglandin-E<sub>2</sub> in microglial cells. In addition, LPS tolerance downregulated the expression of suppressor of cytokine signaling 3, and inducible nitric oxide synthase/nitric oxide; suppressed the LPS-mediated induction of tumor necrosis factor-α, interleukin (IL)-6, and IL-1; and reduced reactive oxygen species production in microglial cells. LPS stimulation increased the levels of the adaptive response–related proteins heme oxygenase-1 and superoxide dismutase 2, and the levels of heme oxygenase-1 (HO-1) enhanced after LPS priming. Systemic administration of low-dose LPS (0.5 mg/kg) to mice for 4 consecutive days attenuated high-dose LPS (5 mg/kg)–induced inflammatory response, microglial activation, and proinflammatory cytokine expression. Moreover, repeated exposure to low-dose LPS suppressed the recruitment of peripheral monocytes or macrophages to brain regions and downregulated the expression of proinflammatory cytokines. Notably, LPS-induced social avoidance behaviors in mice were mitigated by immune tolerance. In conclusion, immune tolerance may reduce proinflammatory cytokine expression and reactive oxygen species production. Our findings provide insights into the effects of endotoxin tolerance on innate immune cells and social behaviors.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 225-235"},"PeriodicalIF":3.5,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S134786132400015X/pdfft?md5=c68a625a9686dc84d90f383eda9be5f6&pid=1-s2.0-S134786132400015X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139738712","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

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus 通过恢复 GABA/谷氨酸信号传导和海马体的神经可塑性，激活 σ-1 受体减轻雌激素戒断诱发的小鼠焦虑/抑郁样行为

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-09 DOI: 10.1016/j.jphs.2024.02.003

Peng Ren , Jing-Ya Wang , Hong-Lei Chen , Yue Wang , Lin-Yu Cui , Jing-Yao Duan , Wen-Zhi Guo , Yong-Qi Zhao , Yun-Feng Li

{"title":"Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus","authors":"Peng Ren , Jing-Ya Wang , Hong-Lei Chen , Yue Wang , Lin-Yu Cui , Jing-Yao Duan , Wen-Zhi Guo , Yong-Qi Zhao , Yun-Feng Li","doi":"10.1016/j.jphs.2024.02.003","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.02.003","url":null,"abstract":"<div><p>Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 236-245"},"PeriodicalIF":3.5,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000124/pdfft?md5=551e7d6413187bfae0882225c67467a0&pid=1-s2.0-S1347861324000124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139738713","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

Analyses of the onset mechanisms of cardio-stimulatory action by aciclovir 阿昔洛韦对心脏刺激作用的起效机制分析

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-08 DOI: 10.1016/j.jphs.2024.02.005

Ai Goto , Ryuichi Kambayashi , Koki Chiba , Makoto Shinozaki , Kiryu Moritani , Hiroko Izumi-Nakaseko , Yoshinori Takei , Akira Hirasawa , Atsushi Sugiyama

{"title":"Analyses of the onset mechanisms of cardio-stimulatory action by aciclovir","authors":"Ai Goto , Ryuichi Kambayashi , Koki Chiba , Makoto Shinozaki , Kiryu Moritani , Hiroko Izumi-Nakaseko , Yoshinori Takei , Akira Hirasawa , Atsushi Sugiyama","doi":"10.1016/j.jphs.2024.02.005","DOIUrl":"10.1016/j.jphs.2024.02.005","url":null,"abstract":"<div><p>Cardio-stimulatory actions of aciclovir have been considered to primarily depend on the sympathetically-mediated reflex resulting from its hypotensive effect. To further clarify onset mechanisms of the cardio-stimulatory actions, we initially studied them using isoflurane-anesthetized dogs under thorough β<sub>1</sub>-adrenoceptor blockade with atenolol (1 mg/kg, i.v.) (n = 4). Aciclovir (20 mg/kg/10 min, i.v.) decreased mean arterial blood pressure by 10 mmHg, whereas it increased heart rate by 10 bpm and maximum upstroke velocity of ventricular pressure by 928 mmHg/s, and shortened AH interval by 2 ms, indicating that cardio-stimulatory actions were not totally abolished by β<sub>1</sub>-adrenoceptor blockade. Then, unknown mechanisms of cardio-stimulatory action were explored. Since aciclovir has a similar chemical structure to theophylline, in silico molecular docking simulation was performed, indicating aciclovir as well as theophylline possesses strong likelihood of interactions with phosphodiesterase 1A, 1C and 3A. Indeed, aciclovir inhibited phosphodiesterase 1A derived from the bovine heart (n = 4), moreover it exerted positive chronotropic action on the atrial tissue preparation of rats along with an increase of tissue cyclic AMP concentration (n = 4). These results indicate that cardio-stimulatory actions of aciclovir could result from not only hypotension-induced, reflex-mediated increase of sympathetic tone but also its inhibitory effects on phosphodiesterase in the heart.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 294-300"},"PeriodicalIF":3.5,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000148/pdfft?md5=1ad5852b68e34577972680fdb6f76f61&pid=1-s2.0-S1347861324000148-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139827629","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

Presynaptic inhibition of excitatory synaptic transmission from the calcitonin gene-related peptide-containing parabrachial neurons to the central amygdala in mice – unexpected influence of systemic inflammation thereon 小鼠从含降钙素基因相关肽的杏仁核旁神经元到中央杏仁核的兴奋性突触传递的突触前抑制--全身炎症对此的意外影响

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2024-02-05 DOI: 10.1016/j.jphs.2024.02.004

Naoko Sato , Yukari Takahashi , Yae K. Sugimura , Fusao Kato

{"title":"Presynaptic inhibition of excitatory synaptic transmission from the calcitonin gene-related peptide-containing parabrachial neurons to the central amygdala in mice – unexpected influence of systemic inflammation thereon","authors":"Naoko Sato , Yukari Takahashi , Yae K. Sugimura , Fusao Kato","doi":"10.1016/j.jphs.2024.02.004","DOIUrl":"https://doi.org/10.1016/j.jphs.2024.02.004","url":null,"abstract":"<div><p>The monosynaptic connection from the lateral parabrachial nucleus (LPB) to the central amygdala (CeA) serves as a fundamental pathway for transmitting nociceptive signals to the brain. The LPB receives nociceptive information from the dorsal horn and spinal trigeminal nucleus and sends it to the “nociceptive” CeA, which modulates pain-associated emotions and nociceptive sensitivity. To elucidate the role of densely expressed mu-opioid receptors (MORs) within this pathway, we investigated the effects of exogenously applied opioids on LPB-CeA synaptic transmission, employing optogenetics in mice expressing channelrhodopsin-2 in LPB neurons with calcitonin gene-related peptide (CGRP). A MOR agonist ([D-Ala<sup>2</sup>,N–Me-Phe<sup>4</sup>,Glycinol<sup>5</sup>]-enkephalin, DAMGO) significantly reduced the amplitude of light-evoked excitatory postsynaptic currents (leEPSCs), in a manner negatively correlated with an increase in the paired-pulse ratio. An antagonist of MORs significantly attenuated these effects. Notably, this antagonist significantly increased leEPSC amplitude when applied alone, an effect further amplified in mice subjected to lipopolysaccharide injection 2 h before brain isolation, yet not observed at the 24-h mark. We conclude that opioids could shut off the ascending nociceptive signal at the LPB-CeA synapse through presynaptic mechanisms. Moreover, this gating process might be modulated by endogenous opioids, and the innate immune system influences this modulation.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"154 4","pages":"Pages 264-273"},"PeriodicalIF":3.5,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1347861324000136/pdfft?md5=fc87a4c71512f61d7cec4f5c1a2ac6d4&pid=1-s2.0-S1347861324000136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139748420","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