Neuropharmacology最新文献

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Oxytocin enhances acquisition in a social trust task in mice, whereas both oxytocin and its antagonist block trust violation learning 催产素能增强小鼠在社会信任任务中的习得,而催产素及其拮抗剂都能阻止信任缺失的学习。
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-26 DOI: 10.1016/j.neuropharm.2025.110389
Samuel Budniok , Zsuzsanna Callaerts-Vegh , Marian Bakermans-Kranenburg , Guy Bosmans , Rudi D'Hooge
{"title":"Oxytocin enhances acquisition in a social trust task in mice, whereas both oxytocin and its antagonist block trust violation learning","authors":"Samuel Budniok ,&nbsp;Zsuzsanna Callaerts-Vegh ,&nbsp;Marian Bakermans-Kranenburg ,&nbsp;Guy Bosmans ,&nbsp;Rudi D'Hooge","doi":"10.1016/j.neuropharm.2025.110389","DOIUrl":"10.1016/j.neuropharm.2025.110389","url":null,"abstract":"<div><div>The complex effects of the neurohormone oxytocin (OT) on socio-cognitive phenomena have recently been proposed to be complementary with safety learning, where a stimulus acquires safety-predicting properties when it predicts non-occurrence of an aversive event. OT may enhance salience of safety stimuli and promote positive social behavior, such as trust, by reducing anxiety and stress. Complementary, OT may reduce the ability to modulate previously learned behaviors based on new, contradicting information. This occurs through its attenuation of prediction error (PE)—the discrepancy between expectations and actual outcomes. In the current study, we modulated OT receptor (OTR) activity by administering an agonist (OT) and antagonist (cligosiban, CL), and subjected male and female mice to our social transmission of food preference (STFP) protocol to assess social safety learning. STFP is based on the observation that food neophobia of rodents is attenuated when a conspecific signals the safety of the food. We used safe food preference as putative murine homologue of human trust acquisition<em>,</em> and modeled trust violation (PE) using lithium chloride (LiCl)-induced food aversion after social interaction. In males, results revealed that OT enhanced trust acquisition, whereas both OT and its antagonist CL similarly blocked trust violation learning. None of the manipulations affected female behavior. Our findings highlight the complexities of OT's role in social behavior, emphasizing caution in therapeutic manipulations of this system.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110389"},"PeriodicalIF":4.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Omega-3-Enriched Fish oil reduces the chemotherapy-induced peripheral neuropathy in mice 富含omega -3的鱼油可减少小鼠化疗引起的周围神经病变
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-25 DOI: 10.1016/j.neuropharm.2025.110384
Jessica Melato , Fernanda Capitanio Goldoni , Larissa Benvenutti , Thiago Patrício Corrêa , Aline Pertile Remor , Karina Giacomini Varela , Luis Carlos Stoeberl , Gabriel Gripp Fernandes , Giulia de Lima Rasga , Giselle Fazzioni Passos , Miriam Anders Apel , Luiz Carlos Klein-Junior , José Roberto Santin , Robson da Costa , Nara Lins Meira Quintão
{"title":"Omega-3-Enriched Fish oil reduces the chemotherapy-induced peripheral neuropathy in mice","authors":"Jessica Melato ,&nbsp;Fernanda Capitanio Goldoni ,&nbsp;Larissa Benvenutti ,&nbsp;Thiago Patrício Corrêa ,&nbsp;Aline Pertile Remor ,&nbsp;Karina Giacomini Varela ,&nbsp;Luis Carlos Stoeberl ,&nbsp;Gabriel Gripp Fernandes ,&nbsp;Giulia de Lima Rasga ,&nbsp;Giselle Fazzioni Passos ,&nbsp;Miriam Anders Apel ,&nbsp;Luiz Carlos Klein-Junior ,&nbsp;José Roberto Santin ,&nbsp;Robson da Costa ,&nbsp;Nara Lins Meira Quintão","doi":"10.1016/j.neuropharm.2025.110384","DOIUrl":"10.1016/j.neuropharm.2025.110384","url":null,"abstract":"<div><div>Cancer is a leading cause of mortality and morbidity worldwide and conventional chemotherapy frequently induce irreversible adverse effects in patients. Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of both paclitaxel (PTX) and oxaliplatin (OXA) chemotherapies, affecting approximately 30–50% of patients. As cancer survival rates have improved, the efforts of scientific community to develop new strategies for preventing CIPN are also growing. This study presents the effects of omega-3 (ω-3)-enriched fish oil supplementation on the hypersensitivity induced by PTX or OXA in mice. GC-MS analysis of the fish oil revealed an amount of EPA and DHA corresponding to 55.2% and 37.4% of total oil composition, respectively. The thirty-day supplementation with the fish oil prevented the cold hypersensitivity induced by the acute OXA injection protocol, with reduction of spinal cord microglia activation, as well as decreased levels of cytokines and BDNF in the spinal cord and brain. A similar effect was observed with the chronic OXA administration, reducing both mechanical and thermal hypersensitivity. The fish oil also prevented PTX-induced neuropathy, accompanied by a reduction in cytokine levels. It is important to mention that biochemical parameters such as total cholesterol, triglycerides and glucose were also normalised. The fish oil supplementation prevented the development of hypersensitivity in both OXA and PTX models, with reduced neuroinflammation likely being the main mechanism behind this effect. The fish oil supplementation, either before or during chemotherapy, could be an important ally to prevent and treat CIPN, improving the patients’ quality of life post-cancer treatment.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110384"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Vortioxetine attenuates rotenone-induced enteric neuroinflammation via modulation of the TLR2/S100B/RAGE signaling pathway in a rat model of Parkinson's disease 在帕金森病大鼠模型中,Vortioxetine通过调节TLR2/S100B/RAGE信号通路减轻鱼藤酮诱导的肠内神经炎症
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-25 DOI: 10.1016/j.neuropharm.2025.110385
Dilara Nemutlu Samur , Sendegül Yıldırım , Erkan Maytalman , Merzuka Kalay , Gamze Tanrıöver , Gül Özbey
{"title":"Vortioxetine attenuates rotenone-induced enteric neuroinflammation via modulation of the TLR2/S100B/RAGE signaling pathway in a rat model of Parkinson's disease","authors":"Dilara Nemutlu Samur ,&nbsp;Sendegül Yıldırım ,&nbsp;Erkan Maytalman ,&nbsp;Merzuka Kalay ,&nbsp;Gamze Tanrıöver ,&nbsp;Gül Özbey","doi":"10.1016/j.neuropharm.2025.110385","DOIUrl":"10.1016/j.neuropharm.2025.110385","url":null,"abstract":"<div><div>Emerging evidence suggests that gastrointestinal dysfunction and enteric nervous system pathology play a critical role in the early stages of Parkinson's disease. Considering the bidirectional relationship between gastrointestinal symptoms and mood disorders, this study aimed to elucidate the effects and possible mechanisms of action of vortioxetine, a serotonergic antidepressant, on the pathophysiological changes induced by rotenone in the enteroglial cells. α-synuclein, phosphorylated α-synuclein, TLR2, S100B and RAGE expression were detected in duodenal tissues of rats administered rotenone (2 mg/kg/day, s.c.) and/or vortioxetine (10 mg/kg/day, s.c.) for 28 days. For the mechanism of action studies, rat-derived enteroglial cells were treated with rotenone (10 μM) and/or vortioxetine (5 μM or 1 μM) for 24 h. The effects of vortioxetine were evaluated in the presence of the TLR2 antagonist C29, RAGE antagonist FPS-ZM1 and the S100B inhibitor pentamidine. TLR2, S100B, RAGE, and NFκB mRNA levels and proinflammatory cytokines via RT-qPCR and ELISA. Our results demonstrate that rotenone treatment significantly increased α-synuclein, pS129-α-synuclein, TLR2, and S100B expression while reducing RAGE levels, indicating marked enteric pathology. Vortioxetine administration attenuated these effects, reducing α-synuclein accumulation and proinflammatory markers. <em>In vitro</em>, rotenone impaired glial responses, decreasing S100B, RAGE, and NFκB markers, while vortioxetine improved these responses, promoting resynthesis of inflammatory molecules. Notably, S100B, NFκB, and cytokine levels (TNF-α, IL-1β, IL-6) were affected by C29, FPS-ZM1, and pentamidine pretreatments. Thus, vortioxetine is thought to have beneficial effects on rotenone-induced pathological changes in EGCs, and some of these effects are thought to be mediated by the TLR2/S100B/RAGE pathway.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110385"},"PeriodicalIF":4.6,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Red nucleus mGluR4 and mGluR8 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β 红核mGluR4和mGluR8通过抑制TNF-α和IL-1β的表达来抑制痛觉和神经性疼痛的发生
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-24 DOI: 10.1016/j.neuropharm.2025.110387
Ya-Li Xu , Yu-Tong Xia , Miao-Miao Zhang , Yue-Jia Li , Xiao-Xia Tao , Ke Li , Qing-Qing Yang , Xue Tian , Ji-Bo Wu , Ya-Ting Shi , Jun-Yang Wang , Xiao-Yan Zeng
{"title":"Red nucleus mGluR4 and mGluR8 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β","authors":"Ya-Li Xu ,&nbsp;Yu-Tong Xia ,&nbsp;Miao-Miao Zhang ,&nbsp;Yue-Jia Li ,&nbsp;Xiao-Xia Tao ,&nbsp;Ke Li ,&nbsp;Qing-Qing Yang ,&nbsp;Xue Tian ,&nbsp;Ji-Bo Wu ,&nbsp;Ya-Ting Shi ,&nbsp;Jun-Yang Wang ,&nbsp;Xiao-Yan Zeng","doi":"10.1016/j.neuropharm.2025.110387","DOIUrl":"10.1016/j.neuropharm.2025.110387","url":null,"abstract":"<div><div>Metabotropic glutamate receptors (mGluR) participate in pain modulation and mediate different effects in nociceptive stimuli, relying on the receptor subtype activated and its anatomical location. Here, we addressed the functions of mGluR Ⅲ group (mGluR4, mGluR6, mGluR7, and mGluR8) in the red nucleus (RN) in nociception and the development of neuropathic pain induced by spared nerve injury (SNI) using male rats. Our results showed that mGluR4, mGluR7, and mGluR8, except for mGluR6, were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the expressions of mGluR4 and mGluR8 rather than mGluR7 were reduced in the RN contralateral to the nerve lesion. Unilateral administration of mGluR Ⅲ antagonist MSOP to the RN of normal rats decreased the PWT of contralateral hindpaw and evoked pronounced mechanical allodynia, which was blocked by mGluR4 agonist VU0155041 or mGluR8 agonist AZ12216052 instead of mGluR7 agonist AMN082. Moreover, administration of VU0155041 or AZ12216052 to the RN contralateral to the nerve injury at 2 weeks post-SNI alleviated SNI-induced neuropathic pain. Further studies indicated that administration of MSOP to the RN of normal rats increased the expressions of nociceptive factors TNF-α and IL-1β, which were blocked by VU0155041 or AZ12216052 instead of AMN082. Additionally, administration of VU0155041 or AZ12216052 to the RN at 2 weeks post-SNI inhibited the overexpressions of TNF-α and IL-1β induced by SNI. These findings suggest that red nucleus mGluR4 and mGluR8 instead of mGluR7 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110387"},"PeriodicalIF":4.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Microglial phagocytosis and regulatory mechanisms: Key players in the pathophysiology of depression 小胶质细胞吞噬和调节机制:抑郁症病理生理的关键参与者。
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-22 DOI: 10.1016/j.neuropharm.2025.110383
Man Wang , Guimin Jin , Tingting Duan , Run Li , Yubin Gao , Ming Yu , Yuhao Xu
{"title":"Microglial phagocytosis and regulatory mechanisms: Key players in the pathophysiology of depression","authors":"Man Wang ,&nbsp;Guimin Jin ,&nbsp;Tingting Duan ,&nbsp;Run Li ,&nbsp;Yubin Gao ,&nbsp;Ming Yu ,&nbsp;Yuhao Xu","doi":"10.1016/j.neuropharm.2025.110383","DOIUrl":"10.1016/j.neuropharm.2025.110383","url":null,"abstract":"<div><div>Depression is a globally prevalent emotional disorder with a complex pathophysiology. Microglia are resident immune cells in the central nervous system, playing crucial roles in regulating inflammation, synaptic plasticity, immune phagocytosis, and other functions, thereby exerting significant impacts on neuropsychiatric disorders like depression. Increasing research indicates that abnormal phagocytic function of microglia in the brain is involved in depression, showing excessive or insufficient phagocytosis in different states. Here, we have provided a review of the signaling molecules involved in microglial phagocytosis in depression, including “eat me” signals such as phosphatidylserine (PS), complement, and “don't eat me” signals such as CD47, CD200 and related receptors. Furthermore, we discuss the regulatory effects of existing pharmaceuticals and dietary nutrients on microglial phagocytosis in depression, emphasizing the need for tailored modulation based on the varying phagocytic states of microglia. This review aims to facilitate a deeper understanding of the role of microglial phagocytosis in depression and provide a roadmap for potential therapeutic strategies for depression targeting microglial phagocytosis.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110383"},"PeriodicalIF":4.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Hippocampus muscarinic M4 receptor mRNA expression may influence central cholinergic activity, causing fear memory strengthening by peripheral adrenaline 海马毒蕈碱M4受体mRNA表达可能影响中枢胆碱能活性,引起外周肾上腺素增强恐惧记忆。
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-21 DOI: 10.1016/j.neuropharm.2025.110382
Ana Oliveira , Márcia Azevedo , Rafaela Seixas , Soraia Silva , Raquel Martinho , Paula Serrão , Elisabete Silva , Mónica Moreira-Rodrigues
{"title":"Hippocampus muscarinic M4 receptor mRNA expression may influence central cholinergic activity, causing fear memory strengthening by peripheral adrenaline","authors":"Ana Oliveira ,&nbsp;Márcia Azevedo ,&nbsp;Rafaela Seixas ,&nbsp;Soraia Silva ,&nbsp;Raquel Martinho ,&nbsp;Paula Serrão ,&nbsp;Elisabete Silva ,&nbsp;Mónica Moreira-Rodrigues","doi":"10.1016/j.neuropharm.2025.110382","DOIUrl":"10.1016/j.neuropharm.2025.110382","url":null,"abstract":"<div><div>Adrenaline (Ad) strengthens contextual fear memory by increasing blood glucose, possibly enhancing hippocampus acetylcholine synthesis. Nevertheless, it is unclear if peripheral Ad influences the cholinergic system, contributing to contextual fear memory strengthening. We aimed to evaluate whether peripheral Ad alters muscarinic receptor expression and if the cholinergic system is involved in peripheral Ad contextual fear memory strengthening effect.</div><div>Wild-type (WT) and Ad-deficient male mice (129 × 1/SvJ) underwent a fear conditioning procedure followed by intraperitoneal pre-training and pre-context administration of Ad (0.1 mg/kg), atropine (10 mg/kg), methylatropine (0.5 mg/kg), Ad (0.1 mg/kg) plus atropine (10 mg/kg) or vehicle (NaCl, 0.9%). Shock responsiveness and freezing behaviour were accessed. Hippocampal M<sub>1</sub>, M<sub>2</sub>, and M<sub>4</sub> mRNA expression were evaluated.</div><div>Ad-deficient mice presented decreased hippocampal muscarinic M<sub>4</sub> subtype receptor mRNA expression compared to WT mice. In Ad-administered Ad-deficient mice, hippocampal muscarinic M<sub>4</sub> subtype receptor mRNA expression increased compared with vehicle-administered Ad-deficient mice. On the context day, atropine-administered WT mice presented decreased freezing behaviour compared to vehicle or methylatropine-administered WT mice. Moreover, Ad plus atropine-administered Ad-deficient mice led to decreased freezing behaviour compared to Ad-administered Ad-deficient mice.</div><div>In conclusion, Ad-deficient mice's contextual fear memory impairment was associated with hippocampal muscarinic M<sub>4</sub> subtype receptor down expression, which was reversed by Ad. This may be related to contextual fear memory consolidation or retrieval induced by peripheral Ad. Furthermore, the effect of Ad contextual fear memory might be due to increased hippocampus muscarinic subtype M<sub>4</sub> expression, which may contribute to increased cholinergic activity in the central nervous system.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110382"},"PeriodicalIF":4.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Calcium imaging of central amygdala activity after escalation of fentanyl self-administration 芬太尼自我给药升级后中央杏仁核活动的钙显像。
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-21 DOI: 10.1016/j.neuropharm.2025.110370
Samantha G. Malone , Navid S. Tavakoli , Peggy S. Keller , Michael T. Bardo , Pavel I. Ortinski
{"title":"Calcium imaging of central amygdala activity after escalation of fentanyl self-administration","authors":"Samantha G. Malone ,&nbsp;Navid S. Tavakoli ,&nbsp;Peggy S. Keller ,&nbsp;Michael T. Bardo ,&nbsp;Pavel I. Ortinski","doi":"10.1016/j.neuropharm.2025.110370","DOIUrl":"10.1016/j.neuropharm.2025.110370","url":null,"abstract":"<div><div>The central amygdala (CeA) is involved in opioid relapse-associated behaviors. This study determined if escalation of fentanyl intake as modeled by long-access (LgA) self-administration (SA) alters <em>ex vivo</em> neuronal activity in CeA in response to fentanyl during acute withdrawal and protracted abstinence. Adult male and female Sprague-Dawley rats were trained to self-administer fentanyl or saline across 7 daily 1-h short access (ShA) sessions, followed by 21 6-h long access (LgA) sessions. Following acute (17 h) or protracted (30 days) withdrawal, withdrawal signs were assessed and rats were euthanized for CeA calcium imaging in brain slices. Fentanyl rats demonstrated reduced basal frequency of activity after 30 days withdrawal, but not after 17 h withdrawal. Regardless of SA group, acute fentanyl application in slices reduced activity (frequency, duration, active cell number) of CeA neurons. In acute withdrawal, the magnitude to which acute fentanyl suppressed CeA neuronal activity was smaller in fentanyl SA rats, relative to saline SA controls. However, the magnitude of acute fentanyl effect on suppression of CeA activity was greater in fentanyl SA rats (vs. saline SA controls) after protracted abstinence.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110370"},"PeriodicalIF":4.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Serum amyloid A drive microglia shift to a resolving phenotype through Nrf2 血清淀粉样蛋白A通过Nrf2驱动小胶质细胞向解决表型转移。
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-19 DOI: 10.1016/j.neuropharm.2025.110374
Qi Li , Yiwei Huang , Tao Ban , Kexin Chen , Xuechu Zhen , Qijun Dai , Gufang Zhang
{"title":"Serum amyloid A drive microglia shift to a resolving phenotype through Nrf2","authors":"Qi Li ,&nbsp;Yiwei Huang ,&nbsp;Tao Ban ,&nbsp;Kexin Chen ,&nbsp;Xuechu Zhen ,&nbsp;Qijun Dai ,&nbsp;Gufang Zhang","doi":"10.1016/j.neuropharm.2025.110374","DOIUrl":"10.1016/j.neuropharm.2025.110374","url":null,"abstract":"<div><div>Serum amyloid A (SAA) is an acute-phase protein that has been recognized as a diagnostic biomarker for several diseases. However, the functional studies about the effects of SAA on microglial activation seem controversial. Here, we discovered that SAA induces microglial cells polarize to a pro-resolving M2 phenotype by promoting the stability of the transcription factor Nrf2, which specifically regulates microglia towards a pro-resolving phenotype via metabolic reprogramming. Moreover, we identified that the AMPK/mTOR signaling pathway is involved in SAA-induced Nrf2 upregulation. Additionally, SAA protects cultured neuronal cells from MPP<sup>+</sup>-induced damage, and furthermore, local administration of SAA into the substantia nigra significantly attenuated MPTP-induced dopaminergic neuronal loss, thereby improving motor impairments in mice. In conclusion, for the first time we demonstrate SAA regulate microglial activation by promoting Nrf2 stabilization, ultimately protecting dopaminergic neurons and alleviating MPTP-induced PD-like pathology.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"270 ","pages":"Article 110374"},"PeriodicalIF":4.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Inhibition of HCN channels decreases motivation for alcohol and deprivation-induced drinking in alcohol preferring rats 抑制HCN通道降低酒精偏好大鼠的酒精动机和剥夺性饮酒。
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-19 DOI: 10.1016/j.neuropharm.2025.110371
Shivani P. Vaidya , Roberta G. Anversa , Paulo Pinares-Garcia , Leigh C. Walker , Natasha Pracejus , Christopher A. Reid , Andrew J. Lawrence
{"title":"Inhibition of HCN channels decreases motivation for alcohol and deprivation-induced drinking in alcohol preferring rats","authors":"Shivani P. Vaidya ,&nbsp;Roberta G. Anversa ,&nbsp;Paulo Pinares-Garcia ,&nbsp;Leigh C. Walker ,&nbsp;Natasha Pracejus ,&nbsp;Christopher A. Reid ,&nbsp;Andrew J. Lawrence","doi":"10.1016/j.neuropharm.2025.110371","DOIUrl":"10.1016/j.neuropharm.2025.110371","url":null,"abstract":"<div><div>Globally, around 400 million people live with an alcohol use disorder (AUD), yet current treatments available are suboptimal at a population level. Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels are implicated in the modulation of complex motivated behaviours, including reward seeking. Here, we investigated the potential involvement of HCN channels in alcohol reinforcing effects, contributing to alcohol intake and relapse-like drinking following abstinence in iP rats. The functional role of HCN channels in the motivation to acquire alcohol and relapse-like behaviour was tested <em>in vivo</em> through intracerebroventricular (ICV) infusion of a HCN channel inhibitor, ZD7288 prior to operant progressive ratio responding or the alcohol deprivation effect. Acute ICV infusion of ZD7288 (3 μg/5 μL) significantly reduced motivation to acquire alcohol and attenuated the alcohol deprivation effect after 14 days of abstinence, without affecting spontaneous locomotor activity. HCN channels are densely expressed in cholinergic neurons of the medial habenula (mHb), which have been implicated in stress, aversion, and drug/alcohol intake-associated behaviours. To investigate the impact of alcohol on the expression of HCN channels, cholinergic markers and acetylcholine receptors, we performed qPCR on mHb tissue in alcohol-preferring (iP) rats following chronic voluntary alcohol intake or abstinence. qPCR results showed an upregulation of mRNA encoding key ion channels in the mHb following abstinence from chronic voluntary alcohol use. Collectively, these findings suggest that HCN channels contribute to motivation to consume alcohol and relapse-like behaviour during abstinence in iP rats.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"270 ","pages":"Article 110371"},"PeriodicalIF":4.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Spinal astrocyte-derived M-CSF mediates microglial reaction and drives visceral hypersensitivity following DSS-induced colitis 脊髓星形胶质细胞来源的M-CSF介导小胶质细胞反应并驱动dss诱导的结肠炎后内脏超敏反应
IF 4.6 2区 医学
Neuropharmacology Pub Date : 2025-02-18 DOI: 10.1016/j.neuropharm.2025.110373
Ke Wu , Shuai Shao , Yu-ting Dong , Yue-ying Liu , Xing-han Chen , Peng Cheng , Xia Qin , Xiao-han Peng , Yong-mei Zhang
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