Journal of pharmacological sciences最新文献_第7页

Medial prefrontal cortex inputs to the dorsomedial striatum regulate motivation for wheel running in male mice 内侧前额叶皮层对背内侧纹状体的输入调节雄性小鼠滚轮跑的动机

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-09-01 Epub Date: 2025-06-17 DOI: 10.1016/j.jphs.2025.06.004

Kazuhei Niitani , Ryoma Nishida , Yu Ogura , Naoya Nishitani, Satoshi Deyama, Katsuyuki Kaneda

{"title":"Medial prefrontal cortex inputs to the dorsomedial striatum regulate motivation for wheel running in male mice","authors":"Kazuhei Niitani , Ryoma Nishida , Yu Ogura , Naoya Nishitani, Satoshi Deyama, Katsuyuki Kaneda","doi":"10.1016/j.jphs.2025.06.004","DOIUrl":"10.1016/j.jphs.2025.06.004","url":null,"abstract":"<div><div>Wheel running is rewarding for rodents, and thus they exhibit strong willingness to engage in it and desire for it, i.e., motivation. Although neural activity in the dorsomedial striatum (DM-Str) has been suggested to be involved in motivation for wheel running, the causal relationship between neural activity and motivation remains unknown. Here, we investigated the role of neural activity in the DM-Str and the mechanisms regulating this activity in motivation for wheel running. Fiber photometry recordings with GCaMP sensors revealed that DM-Str neural activity transiently increased at the initiation of running on running wheels (RWs), whereas it decreased during running. Intra-DM-Str injection of the GABA<sub>A</sub> receptor agonist muscimol or the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist NBQX reduced the number of RW rotations. In the open field test, neither muscimol nor NBQX injection into the DM-Str affected locomotor activity. Additionally, selective chemogenetic inhibition of projections from the medial prefrontal cortex (mPFC) to the DM-Str reduced RW rotation numbers without altering locomotor activity. Together, our findings suggest that DM-Str neural activity, enhanced by glutamatergic projection from the mPFC, plays a critical role in regulating motivation for wheel running.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 1","pages":"Pages 1-7"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Automated analysis of mouse rearing using deep learning 利用深度学习对老鼠饲养进行自动分析

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-09-01 Epub Date: 2025-06-13 DOI: 10.1016/j.jphs.2025.06.002

Naoaki Sakamoto , Masahiro Fukuda , Yusuke Miyazaki , Keisuke Omori , Koji Kobayashi , Takahisa Murata

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Inhibitory effects of schisandrin A on contractions induced by spasmogenic candidates in porcine coronary arteries 五味子素A对猪冠状动脉痉挛候选物引起的收缩的抑制作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-05-24 DOI: 10.1016/j.jphs.2025.05.016

Qianghaodi Hong, Naho Takazakura, Hideaki Ozawa, Sakika Ichihara, Kento Yoshioka, Keisuke Obara, Yoshio Tanaka

{"title":"Inhibitory effects of schisandrin A on contractions induced by spasmogenic candidates in porcine coronary arteries","authors":"Qianghaodi Hong, Naho Takazakura, Hideaki Ozawa, Sakika Ichihara, Kento Yoshioka, Keisuke Obara, Yoshio Tanaka","doi":"10.1016/j.jphs.2025.05.016","DOIUrl":"10.1016/j.jphs.2025.05.016","url":null,"abstract":"<div><div>The inhibitory effects and underlying mechanisms of schisandrin A (SA) on contractions induced by spasmogenic candidates and related chemicals were investigated in porcine coronary arteries (PCAs). SA (10<sup>−5</sup>–10<sup>−4</sup> M) inhibited contractions induced by acetylcholine, histamine, serotonin, U46619 (thromboxane A<sub>2</sub> mimetic), prostaglandin F<sub>2α</sub>, and endothelin-1 in a concentration-dependent manner. The inhibition of acetylcholine-induced contractions by SA was stronger than that by diltiazem, although both SA and diltiazem ultimately achieved similar levels of inhibition against other contractions. SA also inhibited high-KCl-induced contractions in PCAs and suppressed high-KCl-induced increases in intracellular Ca<sup>2+</sup> concentrations in A7r5 cells. However, SA (10<sup>−4</sup> M) did not inhibit SKF-96365-sensitive phenylephrine-induced contractions, despite potently inhibiting high-KCl-induced contraction in the guinea pig thoracic aorta. SA did not strongly inhibit NaF-induced contractions in Ca<sup>2+</sup>-free solution containing 0.2 mM EGTA. Furthermore, SA inhibited muscarinic receptor binding in mouse cerebral cortex and inhibited carbachol-induced increases in intracellular Ca<sup>2+</sup> concentrations in 293T cells expressing muscarinic M<sub>3</sub> receptors. These findings indicate that SA inhibits coronary artery contractions induced by spasmogens primarily through the inhibition of L-type Ca<sup>2+</sup> channels (LCCs) and exerts an anticholinergic and LCC inhibitory effect on acetylcholine-induced contractions.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 343-352"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Targeting CD38 to alleviate brain endothelial cell dysfunction and cognitive impairment in vascular dementia 靶向CD38缓解血管性痴呆患者脑内皮细胞功能障碍和认知障碍

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-05-21 DOI: 10.1016/j.jphs.2025.05.013

Mingjing Yu , Zhi Qi , Jiaxin Zhang , Ziyi Zhang , Jieli Chen , Tao Yan , Zhili Chen

{"title":"Targeting CD38 to alleviate brain endothelial cell dysfunction and cognitive impairment in vascular dementia","authors":"Mingjing Yu , Zhi Qi , Jiaxin Zhang , Ziyi Zhang , Jieli Chen , Tao Yan , Zhili Chen","doi":"10.1016/j.jphs.2025.05.013","DOIUrl":"10.1016/j.jphs.2025.05.013","url":null,"abstract":"<div><div>Vascular dementia (VaD) is a leading cause of cognitive decline, closely associated with cerebrovascular endothelial cell (CEC) dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation. CD38, an enzyme implicated in neuroinflammation and cellular senescence, has emerged as a potential regulator of these pathological processes, yet its role in CEC dysfunction within the context of VaD remains unclear. In this study, we investigated the impact of CD38 on CEC dysfunction using a mouse model of VaD induced by bilateral common carotid artery stenosis (BCAS). Our results demonstrate that BCAS significantly reduces cerebral blood flow (CBF), increases BBB permeability, and induces cognitive deficits, all accompanied by elevated CD38 expression in CECs and heightened levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Notably, treatment with the selective CD38 inhibitor 78c (10 mg/kg, twice daily for 1 month) effectively mitigated these effects, reducing white matter damage, improving CBF, enhancing the expression of CEC tight junction proteins, and decreasing neuroinflammation and BBB disruption. In vitro experiments further revealed that 78c attenuates TNF-α-induced CD38 expression and inflammatory responses in CECs, likely through the NOX4/eNOS aixs. These findings identify CD38 as a crucial mediator of CEC dysfunction in VaD, linking chronic cerebral hypoperfusion to neurovascular damage.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 310-321"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel PDE9 inhibitors, KR39526 and KR39582, attenuate cardiac hypertrophy and fibrosis induced by pressure overload 新型PDE9抑制剂KR39526和KR39582可减轻压力过载引起的心脏肥大和纤维化

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-05-30 DOI: 10.1016/j.jphs.2025.05.015

Jeong Hyun Lee , Hyunjin Park , Seung Hyeong Lee , Su Ah Kim , Jun Young Choi , Chae Jo Lim , Ju-Young Shin , Byung Ho Lee , Kwang-Seok Oh

{"title":"Novel PDE9 inhibitors, KR39526 and KR39582, attenuate cardiac hypertrophy and fibrosis induced by pressure overload","authors":"Jeong Hyun Lee , Hyunjin Park , Seung Hyeong Lee , Su Ah Kim , Jun Young Choi , Chae Jo Lim , Ju-Young Shin , Byung Ho Lee , Kwang-Seok Oh","doi":"10.1016/j.jphs.2025.05.015","DOIUrl":"10.1016/j.jphs.2025.05.015","url":null,"abstract":"<div><div>The natriuretic peptide and cyclic guanosine monophosphate (cGMP) cascade are promising therapeutic target for heart failure. This study evaluated the pharmacological properties and cardioprotective effects of novel phosphodiesterase 9 (PDE9) inhibitors, KR39526 and KR39582, <em>in vitro</em> and <em>in vivo</em>. The potency and selectivity of these compounds were assessed through PDE9 inhibitory activity and subfamily selectivity assays. Functional analyses in cardiomyocytes included calcium mobilization, cellular hypertrophy, and protein expression. The cardioprotective efficacy was investigated using a mouse model of pressure-overload-induced cardiac hypertrophy. KR39526 and KR39582 demonstrated potent PDE9A inhibitory activities (IC<sub>50</sub>: 5 ± 2 nM and 0.4 ± 0.1 nM, respectively) with high selectivity. This inhibition led to concentration-dependent calcium influx through maintaining intracellular cGMP levels and significantly suppressed phenylephrine-induced cardiomyocyte hypertrophy. Oral administration (50 mg·kg-1) of these compounds markedly attenuated cardiac hypertrophy and myocardial fibrosis induced by pressure overload. These results suggest that KR39526 and KR39582, as potent and selective PDE9A inhibitors, have strong potential for exerting anti-hypertrophic and anti-fibrotic effects in heart failure. These compounds can serve as valuable pharmacological tools to elucidate the roles of PDE9A signaling in heart failure pathophysiology and hold significant promise as potential therapeutic agents.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 353-362"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Ferulic acid suppresses guinea pig ileal longitudinal smooth muscle contractions by inhibiting voltage-dependent Ca2+ channels 阿魏酸通过抑制电压依赖性Ca2+通道抑制豚鼠回肠纵向平滑肌收缩

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-05-14 DOI: 10.1016/j.jphs.2025.05.012

Keisuke Obara , Kento Yoshioka , Aya Shimada, Sakika Ichihara, Wakaba Kinami, Futaba Makino, Naho Takazakura, Miwa Enomoto, Yoshio Tanaka

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Retraction notice to “Polyphyllin I inhibits growth and invasion of cisplatin-resistant gastric cancer cells by partially inhibiting CIP2A/PP2A/Akt signaling axis” [J Pharmacol Sci 137 (2018) 305–312] “多酚I对顺铂耐药胃癌细胞生长和侵袭的抑制作用”[J]中国药理学杂志，2018,30(5):555 - 557。

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-03-04 DOI: 10.1016/j.jphs.2025.02.009

Yunfei Zhang , Ping Huang , Xuewen Liu , Yuchen Xiang , Te Zhang , Yezi Wu , Jiaxin Xu , Zhiting Sun , Weiguo Zhen , Liang Zhang , Yuan Si , Ying Liu

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Inhibition of CYP1B1 by miR-200b-3p increases the sensitivity of paclitaxel in hepatocellular carcinoma treatment miR-200b-3p抑制CYP1B1可增加紫杉醇治疗肝癌的敏感性

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-05-21 DOI: 10.1016/j.jphs.2025.05.014

Jiaqi Wang , Jiayi Wu , Haihong Hu , Lushan Yu , Xiaoli Zheng , Su Zeng

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Exposure of Zinc-induced Parkinson's disease-like non-motor and motor symptoms in relation to oxidative/nitrosative stress mediated neurodegeneration in the brain of Drosophila melanogaster 暴露于锌诱导的帕金森病样非运动和运动症状与氧化/亚硝化应激介导的黑腹果蝇大脑神经变性有关

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-05-14 DOI: 10.1016/j.jphs.2025.05.010

Abhishek P.R. Nadiga , K.L. Krishna , Afrasim Moin , Amr Selim Abu Lila , Syed Mohd Danish Rizvi , Sahyadri M. , Suman Pathak , Shahanawaz Syed , El-Sayed Khafagy

{"title":"Exposure of Zinc-induced Parkinson's disease-like non-motor and motor symptoms in relation to oxidative/nitrosative stress mediated neurodegeneration in the brain of Drosophila melanogaster","authors":"Abhishek P.R. Nadiga , K.L. Krishna , Afrasim Moin , Amr Selim Abu Lila , Syed Mohd Danish Rizvi , Sahyadri M. , Suman Pathak , Shahanawaz Syed , El-Sayed Khafagy","doi":"10.1016/j.jphs.2025.05.010","DOIUrl":"10.1016/j.jphs.2025.05.010","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the second most prevalent idiopathic neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to locomotor impairment. Despite extensive research, the etiology of PD remains unclear, and existing experimental models for pharmacological evaluation do not fully replicate the disease's hallmarks, necessitating the development of a cost-effective and reliable alternative. In recent past, Drosophila melanogaster has been utilized as a model organism for various neurodegenerative diseases, including PD. The present study was conceptualized to develop a reliable PD model in the Drosophila by Zinc (Zn<sup>+2</sup>).Chronic exposure to 20 mM Zn<sup>+2</sup> for 7 days exhibited non-motor and motor PD-like symptoms in adult Drosophila flies, with reduced locomotory activity, indicating motor function deficit and reduced olfactory function and courtship behavior, indicating a deficit in non-motor function. These behavioral symptoms were associated with decreased dopamine levels. Furthermore, chronic Zn<sup>+2</sup> exposure resulted in enhanced membrane lipid peroxidation and decreased endogenous antioxidants level in the Drosophila brain. These effects were primarily mediated by oxidative/nitrosative stress pathway. Thus, Zn<sup>2+</sup>-induced PD in Drosophila serves as a cost-effective model for drug discovery, facilitating the screening of potential therapeutic compounds. Additionally, this model offers a valuable platform to investigate the molecular mechanisms underlying PD pathophysiology.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 303-309"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Improved serotonin neuron-specific viral vectors applicable for optogenetic manipulation and recording 改良的5 -羟色胺神经元特异性病毒载体，适用于光遗传操作和记录

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-08-01 Epub Date: 2025-05-08 DOI: 10.1016/j.jphs.2025.05.008

Takuma Noguchi , Harune Hori , Koji Toda , Hisashi Shirakawa , Hitoshi Hashimoto , Kazuki Nagayasu

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