{"title":"Male mice recognize male-emitted ultrasonic vocalizations in a two-choice test via oxytocin signaling","authors":"Tomoya Takemoto , Shotaro Kawano , Rei Endo , Kohei Kitagawa , Yukio Ago , Takefumi Kikusui , Hitoshi Hashimoto , Takanobu Nakazawa","doi":"10.1016/j.jphs.2025.11.001","DOIUrl":"10.1016/j.jphs.2025.11.001","url":null,"abstract":"<div><div>Social behaviors rely on the integration of multiple sensory cues. Among these, ultrasonic vocalizations (USVs) serve as primary auditory cues in rodents. Although the function of USVs has been extensively studied in pup–female and male–female interactions, their role in male–male interactions remain to be elucidated. We tested whether adult male mice recognize male-emitted USVs as social cues using a two-choice playback paradigm. We demonstrated that male mice preferred male-emitted USVs and that oxytocin signaling is essential for perceiving male-emitted USVs. This study provides new insights into the neural mechanisms of male–male social behavior.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"160 1","pages":"Pages 23-28"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518095","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}
{"title":"Development of a quantitative gait analysis in an osteoarthritis rat model using machine learning","authors":"Shinya Takenouchi , Takashi Minato , Masahiro Fukuda , Koji Kobayashi , Takahisa Murata","doi":"10.1016/j.jphs.2025.11.004","DOIUrl":"10.1016/j.jphs.2025.11.004","url":null,"abstract":"<div><div>Quantitative assessment of gait abnormality is essential for osteoarthritis (OA) model. We aimed to establish a low-cost, non-invasive and markerless gait analysis pipeline using machine learning. Rat OA model was induced by intraarticular injection of monosodium iodoacetate, and walking behavior was recorded. Joint coordinates were analyzed using DeepLabCut, and hierarchical clustering based on our summarized features separated OA and healthy animals with high accuracy. Principal coordinates analysis demonstrated significant group separation while preserving intra-group variability. We developed a reproducible and non-biased method for gait analysis in OA rats, which can be applicable for pain and movement disorder models.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"160 1","pages":"Pages 59-63"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681540","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}
{"title":"Bidirectional effects of orexin receptor antagonists on long-term potentiation in the hippocampus of wild type and Alzheimer's disease model mice","authors":"Yoshiaki Ohi , Kazuhiro Hada , Yuki Murata , Daisuke Kodama , Yoshifumi Wakiya","doi":"10.1016/j.jphs.2025.11.003","DOIUrl":"10.1016/j.jphs.2025.11.003","url":null,"abstract":"<div><div>The orexinergic system is dysregulated in patients with Alzheimer's disease (AD). In the present study, we evaluated the effects of chronic administration of dual orexin receptor antagonists, suvorexant (Suv) and lemborexant (Lem), on long-term potentiation (LTP) in the hippocampal CA1 region of wild-type (WT) and APP<sup>NL−G-F</sup> knock-in (APP-KI) mice. LTP was enhanced in APP-KI mice compared with WT mice. Chronic administration of Suv and Lem further potentiated LTP in WT mice. In contrast, in APP-KI mice, Suv moderately and Lem markedly reduced LTP. These findings suggest that orexin receptor antagonists bidirectionally modulate LTP in WT and AD model mice.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"160 1","pages":"Pages 37-40"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518069","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}
{"title":"Feasibility of recent peptide therapy for ischemic stroke: a comprehensive exploration","authors":"Kuo-Feng Tseng , Kuo-Wei Tseng , Hsien-Yin Liao , Pei-Hsien Chen","doi":"10.1016/j.jphs.2025.10.007","DOIUrl":"10.1016/j.jphs.2025.10.007","url":null,"abstract":"<div><div>Ischemic stroke is a prominent cause of disability and mortality worldwide, currently no drug therapy is helpful for post-stroke symptoms; thus, there is a need to develop effective treatment strategies. Peptide medication development has advanced significantly in the recent years and due to its potential to modulate key molecular pathways involved in stroke pathophysiology. This review provides an overview of recent advances in peptide therapy for stroke. These peptides can exert neuroprotective effects by inhibiting excitotoxicity, oxidative stress, and apoptosis, while also promoting neuronal survival and synaptic plasticity. Furthermore, artificial intelligence (AI) with deep learning holds a promising technique in peptide generation by enabling the design of novel peptides with specific binding site of a protein, this may accelerate drug discovery processes through predictive modeling and high-throughput analysis. Overall, peptide therapy holds great potential for improving stroke outcomes and represents a promising avenue for the development of novel stroke treatments.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"160 1","pages":"Pages 1-11"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435317","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}
{"title":"β2 microglobulin promotes pericyte proliferation through toll-like receptor 4","authors":"Yoshino Yonezu , Akiko Uyeda , Hidemi Misawa , Rieko Muramatsu","doi":"10.1016/j.jphs.2025.12.001","DOIUrl":"10.1016/j.jphs.2025.12.001","url":null,"abstract":"<div><div>Pericytes are perivascular cells that contribute to maintaining vascular integrity and central nervous system homeostasis. β<sub>2</sub>-microglobulin (B2M) is a component of the major histocompatibility complex class I molecule; it has recently been implicated in age-related and injury-associated inflammation. Here, we investigated the phenotypic and transcriptomic effects of B2M on mouse brain pericytes <em>in vitro</em>. B2M treatment increased Bromodeoxyuridine (BrdU) incorporation into the cultured pericytes as well as the number of Ki67-positive pericytes. Morphologically, B2M promoted pericyte extension. Toll-like receptor 4 (TLR4), one of the key molecules that regulates B2M function, was involved in the B2M-dependent pericyte proliferation. These findings were consistent with RNA-seq results showing differential expression of genes related to cell proliferation. These results suggest that B2M directly acts on pericytes and regulates part of their functional responses through TLR4 signaling.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"160 1","pages":"Pages 81-89"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733260","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}
Olesia F. Moroz , Viktoriia I. Kravchenko , Alexander V. Zholos
{"title":"Constituents of essential oils as modulators of TRP channels: Focus on cognitive functions, neurodegenerative, and psychological diseases","authors":"Olesia F. Moroz , Viktoriia I. Kravchenko , Alexander V. Zholos","doi":"10.1016/j.jphs.2025.11.007","DOIUrl":"10.1016/j.jphs.2025.11.007","url":null,"abstract":"<div><div>Essential oils have long been recognized for their therapeutic potential, with growing interest in their molecular mechanisms of action in neurological health. Among emerging targets, polymodal Ca<sup>2+</sup>-permeable Transient Receptor Potential (TRP) cation channels have gained particular attention for their roles in neuronal signaling, synaptic plasticity, and modulation of cognitive, neurodegenerative, and psychological disorders. This review explores the ability of essential oil constituents to modulate TRP channels. The major channels to be discussed here include TRPV1, TRPM8, and TRPA1 and some other TRPVs and TRPMs. Some TRPC members have also been reviewed, albeit more briefly. Key bioactive compounds – including menthol, linalool, and eugenol – are highlighted for their ability to interact with TRP channels, while influencing neurophysiological pathways related to learning, memory, neuroinflammation, and emotional regulation. Preclinical evidence suggests these interactions may offer neuroprotective, anxiolytic, and antidepressant effects. However, challenges such as bioavailability, standardization, and safety remain barriers to clinical translation. This review underscores the therapeutic promise of essential oil constituents as modulators of TRP channels and outlines future directions for their integration into neurotherapeutic strategies.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"160 1","pages":"Pages 69-80"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145681539","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}
Jingjing Shi , Caina Ma , Yuexi Liu , Chao Yang , Jinyu Wu , Xiaohong Wang
{"title":"MicroRNA-3473b regulates corticosterone-induced microglial polarization and inflammation through TREM2","authors":"Jingjing Shi , Caina Ma , Yuexi Liu , Chao Yang , Jinyu Wu , Xiaohong Wang","doi":"10.1016/j.jphs.2025.09.002","DOIUrl":"10.1016/j.jphs.2025.09.002","url":null,"abstract":"","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 209-218"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099892","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}
{"title":"Endothelial NLRP3-mediated pyroptosis induces blood-brain barrier and neuronal damage in Huntington's disease models","authors":"Jing Cai , Wenshuang Ji , Peng Liu , Libo Zou","doi":"10.1016/j.jphs.2025.09.003","DOIUrl":"10.1016/j.jphs.2025.09.003","url":null,"abstract":"<div><div>The NLRP3 inflammasome is primarily expressed and activated in microglial and endothelial cells. Extensive research has been conducted on the activation of NLRP3 inflammasomes by microglial cells leading to pyroptosis. However, there have been no reports on the activation of NLRP3 inflammasomes in brain vascular endothelial cells in patients with Huntington's disease (HD) or HD animal models, leading to blood-brain barrier (BBB) disruption. We herein found that BBB leakage increased and the expression of tight junction proteins significantly decreased after transfecting the mutant Huntingtin protein (mHtt) Q74 plasmid into the mouse brain microvascular endothelial cell line bEnd.3. mHtt promoted the activation of NLRP3 by brain vascular endothelial cells, and increased the expression of the pyroptosis-related proteins. This resulted in a decrease in the expression of the NeuN in the brain of hHTT130 transgenic mice. Furthermore, by downregulating <em>NLRP3</em> in Q74-transfected bEnd.3 cells or in hHTT130 mouse brain vascular endothelial cells, BBB disruption and endothelial cell pyroptosis were alleviated, the number of surviving neurons was significantly increased. In conclusion, mHtt can activate the NLRP3 inflammasome in brain microvascular endothelial cells to induce endothelial cell pyroptosis, thereby disrupting the function of the BBB, leading to neuronal damage.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 256-267"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120471","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}
Jun Horizono , Keito Mizumoto , Mary Ann Suico , Shota Kaseda , Yuya Sannomiya , Haruki Tsuhako , Aimi Owaki , Ryoichi Sato , Masahiro Shiraga , Riko Kato , Ryo Kumabe , Tsuyoshi Shuto , Hirofumi Kai
{"title":"Dapagliflozin with losartan but not olmesartan has an add-on protective effect in experimental Alport syndrome","authors":"Jun Horizono , Keito Mizumoto , Mary Ann Suico , Shota Kaseda , Yuya Sannomiya , Haruki Tsuhako , Aimi Owaki , Ryoichi Sato , Masahiro Shiraga , Riko Kato , Ryo Kumabe , Tsuyoshi Shuto , Hirofumi Kai","doi":"10.1016/j.jphs.2025.09.008","DOIUrl":"10.1016/j.jphs.2025.09.008","url":null,"abstract":"<div><div>Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and angiotensin receptor blockers (ARBs) each have renoprotective effects in chronic kidney diseases, including Alport syndrome. Here, we investigated the combination of SGLT2i dapagliflozin and ARBs with different antiproteinuric strength - losartan (weak) and olmesartan (strong) - in <em>Col4a5</em> G5X Alport mice. Dapagliflozin enhanced the renoprotective effect of losartan but not of olmesartan. Olmesartan alone suppressed the decline in renal function and prolonged survival similarly to losartan plus dapagliflozin. These findings suggest that the add-on effectiveness of dapagliflozin varies depending on the ARB, and that their combination needs careful evaluation for maximum benefit.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 252-255"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120421","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}
{"title":"Effects of imeglimin on mitochondrial functions and ischemic brain damage in young and aging rats","authors":"Evelina Paskeviciene, Kristina Skemiene, Katryna Pampuscenko, Silvija Jankeviciute, Vilmante Borutaite","doi":"10.1016/j.jphs.2025.10.001","DOIUrl":"10.1016/j.jphs.2025.10.001","url":null,"abstract":"<div><div>Imeglimin, a novel oral antidiabetic drug, has been suggested to affect mitochondrial functions in some types of cells and tissues, however, it has never been investigated whether aging has an impact on its pharmacological effects in the brain. In this study, we investigated whether imeglimin directly affects functions of brain mitochondria and whether its intraperitoneal injection protects against ischemic brain injury in young, middle-aged and aged Wistar rats. We found that direct addition of imeglimin to mitochondria isolated from young and middle-aged rat brains suppressed oxidative phosphorylation and activities of mitochondrial Complexes I and IV. The opposite, stimulating effect on Complex II activity was observed within the same groups. Injection of imeglimin 24 h before simulated brain ischemia <em>in vitro</em> reduced infarct size only in young and middle-aged rat groups. In the aged rat group, imeglimin did not reduce cerebral infarct size nor directly modulate mitochondrial respiration and activities of the complexes. In conclusion, we provided novel evidence on potential effects of imeglimin in the brain by demonstrating a direct stimulating effect on mitochondrial Complex II activity and age-dependent protective effects against brain injury under <em>in vitro</em> simulated ischemia.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 301-309"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364004","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}