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Maternal exercise during pregnancy: Sex-specific impacts on offspring memory and maternal deprivation effects 怀孕期间的母亲运动:对后代记忆和母亲剥夺效应的性别特异性影响
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-28 DOI: 10.1016/j.neulet.2025.138252
Guilherme Salgado Carrazoni, Pâmela B. Mello-Carpes
{"title":"Maternal exercise during pregnancy: Sex-specific impacts on offspring memory and maternal deprivation effects","authors":"Guilherme Salgado Carrazoni,&nbsp;Pâmela B. Mello-Carpes","doi":"10.1016/j.neulet.2025.138252","DOIUrl":"10.1016/j.neulet.2025.138252","url":null,"abstract":"<div><div>Maternal deprivation (MD) is a well-established paradigm used to study the effects of early-life stress on offspring brain development and behavior, particularly memory. Maternal exercise (ME) during pregnancy has been shown to influence offspring brain development and behavior. Our study examined whether ME protocols—stop, start, reduce, or maintain running during pregnancy—could protect offspring from MD-induced memory deficits and impact hippocampal oxidative balance. Initially, adult Wistar female rats were divided into five groups: non-exercised mothers (NE), mothers who exercised only before pregnancy (PRE), mothers who exercised before and reduced the intensity during pregnancy (RED), mothers who exercised at the same intensity before and during pregnancy (EQUAL), and mothers who started exercise during pregnancy (GEST). After delivery, the groups were subdivided into control (CT) and MD. At 90 days of age, the offspring underwent an object recognition (OR) memory test, and hippocampal lipid peroxidation and catalase (CAT) levels were measured. MD-induced memory deficits in male but not female offspring. Only the male PRE group showed a memory deficit, while all other exercise protocols prevented the MD-induced deficits. MD did not affect hippocampal cell membrane peroxidation, and PRE and EQUAL protocols increased catalase levels compared to NE + CT controls. Our results highlight that maintaining or starting exercise during pregnancy mitigates memory deficits induced by MD, particularly in male offspring.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138252"},"PeriodicalIF":2.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Lithium exacerbates Lafora body formation in the Epm2a-/- Lafora disease mouse model 在Epm2a-/- Lafora病小鼠模型中,锂加剧了Lafora体的形成
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-19 DOI: 10.1016/j.neulet.2025.138250
Jun Wu, Tori C. Lynn , Silvia Nitschke, Sharmistha Mitra, Berge A. Minassian
{"title":"Lithium exacerbates Lafora body formation in the Epm2a-/- Lafora disease mouse model","authors":"Jun Wu,&nbsp;Tori C. Lynn ,&nbsp;Silvia Nitschke,&nbsp;Sharmistha Mitra,&nbsp;Berge A. Minassian","doi":"10.1016/j.neulet.2025.138250","DOIUrl":"10.1016/j.neulet.2025.138250","url":null,"abstract":"<div><div>Lafora disease (LD) is a fatal neurodegenerative epilepsy of teenagers due to accumulations of overlong-branched glycogen (Lafora bodies, LBs) and caused by deficient laforin or its interacting partner malin. While how the laforin-malin complex regulates glycogen chain lengths is unknown, it is known that downregulating the glycogen chain-elongating enzyme glycogen synthase prevents LB formation. Lithium is a longstanding treatment for neuropsychiatric diseases. Lithium was recently shown to lead to glycogen synthase phosphorylation (i.e. inhibition) in rat brains through an unknown pathway. We tested whether lithium can prevent LB formation in laforin-deficient LD mice. We found that in these mice lithium leads to glycogen synthase dephosphorylation (i.e. activation), and increased LBs in hearts of 100% and brains of 40% of treated mice. The latter were all sickly compared to the 60% in whose brains LBs did not increase. These results are generally cautionary regarding therapeutic translatability from rodents to humans where basic mechanisms are unknown. Increased LB formation only in frail mice suggests existence of self-perpetuating processes in LD. Finally, lithium clearly influences glycogen metabolism with outcomes similar to disturbances of the laforin-malin complex. Understanding lithium’s action in glycogen metabolism may aid the understanding of the mechanisms of laforin-malin and LD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138250"},"PeriodicalIF":2.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Enhanced flavoprotein autofluorescence imaging in rats using a combination of thin skull window and skull-clearing reagents 使用薄颅骨窗和颅骨清除试剂组合增强大鼠黄蛋白自身荧光成像
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-17 DOI: 10.1016/j.neulet.2025.138239
Yuto Ogawa , Kazuaki Nagasaka , Daisuke Ishii , Ayane Nagao , Hitomi Ikarashi , Naofumi Otsuru , Hideaki Onishi
{"title":"Enhanced flavoprotein autofluorescence imaging in rats using a combination of thin skull window and skull-clearing reagents","authors":"Yuto Ogawa ,&nbsp;Kazuaki Nagasaka ,&nbsp;Daisuke Ishii ,&nbsp;Ayane Nagao ,&nbsp;Hitomi Ikarashi ,&nbsp;Naofumi Otsuru ,&nbsp;Hideaki Onishi","doi":"10.1016/j.neulet.2025.138239","DOIUrl":"10.1016/j.neulet.2025.138239","url":null,"abstract":"<div><div>Flavoprotein autofluorescence (FA) imaging is a powerful technique for investigating neural activity in vivo. However, its application in rats is limited by the thickness of the intact skull, which reduces light transmission and signal-to-noise ratio (SNR). In this study, we introduce a novel approach that integrates a thin skull window (TSW) with a skull-clearing reagent (CTSW) to enhance FA imaging in rats. The FA signals evoked by somatosensory stimulation were recorded under both TSW and CTSW conditions. The results demonstrate that CTSW significantly improved the SNR of FA signals compared to TSW alone, enabling more precise detection of neural activity. Notably, the enhanced signal clarity facilitated robust imaging in the secondary motor cortex (M2), a region where activity is barely detectable using conventional TSW. By better preserving intracranial physiological conditions than craniotomy, CTSW minimizes postoperative complications and supports longitudinal imaging. Furthermore, this technique may be applicable to other optical imaging modalities, including calcium and vascular imaging. The ability to enhance cortical signal detection while maintaining a minimally invasive preparation positions CTSW as a promising tool for functional mapping and long-term studies in behaving rats.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138239"},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Evaluation of the effect of biperiden (cholinergic muscarinic receptor antagonist) on ethanol self-administration in rats 胆碱能毒蕈碱受体拮抗剂biperiden对大鼠乙醇自我给药作用的评价
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-12 DOI: 10.1016/j.neulet.2025.138240
Paola Palombo , Clarice Ribeiro Lira , Sara Emi Matos Mendes Ferreira Badaro , Lucas Teodoro , Fábio Cardoso Cruz , José Carlos Fernandes Galduróz , Rodrigo Molini Leão
{"title":"Evaluation of the effect of biperiden (cholinergic muscarinic receptor antagonist) on ethanol self-administration in rats","authors":"Paola Palombo ,&nbsp;Clarice Ribeiro Lira ,&nbsp;Sara Emi Matos Mendes Ferreira Badaro ,&nbsp;Lucas Teodoro ,&nbsp;Fábio Cardoso Cruz ,&nbsp;José Carlos Fernandes Galduróz ,&nbsp;Rodrigo Molini Leão","doi":"10.1016/j.neulet.2025.138240","DOIUrl":"10.1016/j.neulet.2025.138240","url":null,"abstract":"<div><div>Evidence from the literature suggests that alcohol use disorder (AUD) is closely associated with alterations in neuronal plasticity and the memory system, related to modifications in muscarinic receptors. The present study aimed to investigate the effects of systemic injection of biperiden, a muscarinic cholinergic antagonist, in experimental protocols of progressive ratio, 24-hour binge alcohol consumption, and reinstatement of context-induced ethanol self-administration. The results demonstrated that biperiden at doses of 5 and 10 mg/kg (i.p.) effectively reduced the animals’ motivation for alcohol consumption, as evidenced by decreased responses on the active lever and a reduction in the last ratio achieved in the progressive ratio protocol. Furthermore, these same doses significantly reduced ethanol consumption in the 24-hour binge protocol. Treatment with biperiden at doses of 1, 5, and 10 mg/kg also attenuated alcohol-seeking behavior after re-exposure to the context associated with ethanol self-administration. These findings suggest that biperiden may have therapeutic potential in the treatment of alcohol use disorder, indicating that modulation of the cholinergic system could be a promising avenue for further investigation.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"856 ","pages":"Article 138240"},"PeriodicalIF":2.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
CRMP2 and its phosphorylation prevent axonal misrouting of the corticospinal tract CRMP2及其磷酸化可防止皮质脊髓束轴突错路
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-06 DOI: 10.1016/j.neulet.2025.138231
Satohiro Takizawa , Yurika Nakanishi , Yumeno Koga , Yuki Yamazaki , Papachan Kolattukudy , Yoshio Goshima , Toshio Ohshima
{"title":"CRMP2 and its phosphorylation prevent axonal misrouting of the corticospinal tract","authors":"Satohiro Takizawa ,&nbsp;Yurika Nakanishi ,&nbsp;Yumeno Koga ,&nbsp;Yuki Yamazaki ,&nbsp;Papachan Kolattukudy ,&nbsp;Yoshio Goshima ,&nbsp;Toshio Ohshima","doi":"10.1016/j.neulet.2025.138231","DOIUrl":"10.1016/j.neulet.2025.138231","url":null,"abstract":"<div><div>During the development of the central nervous system (CNS), the formation of neural circuits such as the corticospinal tract (CST) is crucial to control voluntary movement and is regulated by axonal guidance mechanisms.</div><div>In this study, we examined the role of CRMP2 (Collapsin response mediator protein 2) in the formation of CST. CRMP2, which binds to actin and microtubules to control the cytoskeleton, is a phosphoprotein whose activity depends on its phosphorylated state. To inhibit Cyclin-dependent kinase 5 (Cdk5) phosphorylation, CRMP2 knock-in (<em>crmp2<sup>ki/ki</sup></em>) mice were generated in which the serine residue at position 522 was replaced with alanine. Our results showed that both CRMP2 knock-out (<em>crmp2<sup>-/-</sup></em>) and <em>crmp2<sup>ki/ki</sup></em> mice exhibited higher percentages of CST axons that crossed the midline erroneously than wild-type (WT) mice. However, in mice lacking CRMP1, which is highly homologous to CRMP2, few axons crossed the midline, similar to WT mice. Additionally, <em>crmp2<sup>-/-</sup></em> and <em>crmp2<sup>ki/ki</sup></em> mice showed decreased proportions of independent forelimb movements. These findings emphasize that CRMP2 and its phosphorylation are necessary for proper CST formation in the mouse CNS.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138231"},"PeriodicalIF":2.5,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Brain AMPK signaling improves intestinal barrier function through brain orexin and the vagal pathway in rats 脑AMPK信号通过脑促食欲素和迷走神经通路改善大鼠肠道屏障功能
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-01 DOI: 10.1016/j.neulet.2025.138208
Takuya Funayama , Tsukasa Nozu , Masatomo Ishioh , Chihiro Sumi , Takeshi Saito , Mayumi Hatayama , Masayo Yamamoto , Motohiro Shindo , Shuichiro Takahashi , Toshikatsu Okumura
{"title":"Brain AMPK signaling improves intestinal barrier function through brain orexin and the vagal pathway in rats","authors":"Takuya Funayama ,&nbsp;Tsukasa Nozu ,&nbsp;Masatomo Ishioh ,&nbsp;Chihiro Sumi ,&nbsp;Takeshi Saito ,&nbsp;Mayumi Hatayama ,&nbsp;Masayo Yamamoto ,&nbsp;Motohiro Shindo ,&nbsp;Shuichiro Takahashi ,&nbsp;Toshikatsu Okumura","doi":"10.1016/j.neulet.2025.138208","DOIUrl":"10.1016/j.neulet.2025.138208","url":null,"abstract":"<div><div>Leaky gut, an increased intestinal permeability, has been described in many diseases. We have recently demonstrated that neuropeptides such as orexin in the brain improved leaky gut, suggesting that the brain is involved in maintaining intestinal barrier function. It has been suggested that AMPK in the hypothalamus play a role in food intake. Because the hypothalamus is involved in the regulation of not only feeding behavior but also gut function, the present study was performed to clarify a hypothesis that AMPK in the brain regulate gut barrier function. Colonic permeability was determined by quantifying the absorbed Evans blue within the colonic tissue in rats. Intracisternal AICAR, an AMPK activator, could reduce LPS-induced colonic hyperpermeability while peripherally administered AICAR failed to change it. The improvement of colonic hyperpermeability by intracisternal AICAR was blocked by intracisternal but not subcutaneous compound C, AMPK inhibitor, atropine or vagotomy. The improvement of colonic hyperpermeability by intracisternal AICAR was blocked by intracisternal orexin receptor antagonist but not oxytocin or GLP-1 receptor antagonist. Intracisternal compound C prevented brain oxytocin or GLP-1 but not orexin-induced improvement of colonic hyperpermeability. These results suggest that activation of brain AMPK is capable of reducing colonic hyperpermeability through brain orexin signaling and the vagus nerve. In addition, endogenous AMPK in the brain may mediate the oxytocin or GLP-induced improvement of colonic hyperpermeability. We would suggest that improvement of leaky gut by activation of brain AMPK may play a role in leaky gut-related diseases.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"854 ","pages":"Article 138208"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
EEG alpha power during creative ideation of graphic symbols 图形符号创造性思维过程中的脑电图α能量。
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-01 DOI: 10.1016/j.neulet.2025.138221
Evelyn Cordero , Eugenio Rodríguez , Paulo Barraza
{"title":"EEG alpha power during creative ideation of graphic symbols","authors":"Evelyn Cordero ,&nbsp;Eugenio Rodríguez ,&nbsp;Paulo Barraza","doi":"10.1016/j.neulet.2025.138221","DOIUrl":"10.1016/j.neulet.2025.138221","url":null,"abstract":"<div><div>Graphic symbolic creation—transforming abstract concepts into visual forms—is a cognitively complex and uniquely human skill. Neurophysiological evidence suggests that oscillatory alpha activity is correlated with visual-figurative creative thinking. However, whether alpha oscillations play a functional role in generating graphic symbols remains unclear. To address this issue, we compared the EEG alpha power of 40 healthy adults while ideating creative and conventional graphic symbols representing an abstract concept’s meaning (e.g., the word ’peace’). Our results revealed that the ideation of graphic symbols elicited alpha synchronization, with higher levels in the conventional compared to the creative condition, mainly over frontal-central, frontal-temporal, parietal-occipital, and occipital regions. Furthermore, we observed greater alpha synchronization in the right hemisphere than in the left across both conditions, particularly between temporal, central-parietal, and parietal electrodes. This asymmetry extended to central electrodes in the creative condition, while in the conventional condition, it was more pronounced over parietal-occipital regions. Finally, we also found that frontal and occipital alpha synchronization during the creative ideation phase predicted the subsequent originality scores of the graphic symbols produced. Together, these findings enhance our understanding of the dynamics of oscillatory alpha activity during graphic symbol creation, shedding light on how the interaction between inhibitory top-down control mechanisms and cognitive flexibility processes facilitates the transformation of abstract concepts into visual forms. These findings provide new insights into the neural processes underlying this uniquely human ability.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138221"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
MiR-30b-5p alleviates trigeminal neuralgia induced by chronic constriction injury of the infraorbital nerve by regulating the voltage-gated sodium channel Nav1.3 in rats MiR-30b-5p通过调节电压门控钠通道Nav1.3减轻大鼠眶下神经慢性收缩损伤所致三叉神经痛。
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-01 DOI: 10.1016/j.neulet.2025.138223
Tingting Hu , Mengci Shao , Jiajia Liu , Xiaorong Yan , Liecheng Wang , Yuanyin Wang , Wenhua Xu
{"title":"MiR-30b-5p alleviates trigeminal neuralgia induced by chronic constriction injury of the infraorbital nerve by regulating the voltage-gated sodium channel Nav1.3 in rats","authors":"Tingting Hu ,&nbsp;Mengci Shao ,&nbsp;Jiajia Liu ,&nbsp;Xiaorong Yan ,&nbsp;Liecheng Wang ,&nbsp;Yuanyin Wang ,&nbsp;Wenhua Xu","doi":"10.1016/j.neulet.2025.138223","DOIUrl":"10.1016/j.neulet.2025.138223","url":null,"abstract":"<div><div>Nav1.3 is a tetrodotoxin-sensitive voltage-gated sodium channel isoform encoded by SCN3A, the abnormal expression of which plays a crucial role in the generation of ectopic discharge, as well as being associated with allodynia and hyperalgesia. Using bioinformatics analysis, we showed that miR-30b-5p directly targets SCN3A. We aimed to explore whether miR-30b-5p can participate in trigeminal neuralgia (TN) in rats by regulating the expression of Nav1.3. The rat TN model was constructed through infraorbital nerve-chronic constriction injury (ION-CCI), which was verified by measuring the change in mechanical threshold and the expression of activating transcription factor 3 (a marker of nerve damage) in the trigeminal ganglia (TG). The expression of miR-30b-5p in postoperative TG was downregulated, whereas that of Nav1.3 was upregulated in rats subjected to ION-CCI. Overexpression of miR-30b-5p repressed the expression of Nav1.3 in TG and alleviated ION-CCI-induced TN. MiR-30b-5p targets to regulate the expression of SCN3A, thereby reducing or aggravating TN. Therefore, miR-30b-5p may be a novel therapeutic target for neuropathic pain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138223"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Evidence for effective suppression of INa and IK(DR) by AS2034178 (bis{2-[(4-{(4′-(2-hydroxyethoxy)-2′-methyl[1,1′-biphenyl]-3-yl)methoxy}phenyl]methyl]-3,5-dioxo-1,2,4-oxadiazolidin-4-ide} tetrahydrate), an agonist of free fatty acid receptor 游离脂肪酸受体激动剂AS2034178 (bis{2-[(4-{(4'-(2-羟基乙氧基)-2'-甲基[1,1'-联苯]-3-基)甲氧基}苯基]甲基]-3,5-二氧基-1,2,4-恶二唑烷-4-ide}四水合物)有效抑制INa和IK(DR)的证据。
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-04-01 DOI: 10.1016/j.neulet.2025.138222
Chih-Ju Chou , Chi-Wai Cheung , Chien-Ching Lee , Sheng-Nan Wu , Rasa Liutkeviciene , Vita Rovite , Edmund Cheung So
{"title":"Evidence for effective suppression of INa and IK(DR) by AS2034178 (bis{2-[(4-{(4′-(2-hydroxyethoxy)-2′-methyl[1,1′-biphenyl]-3-yl)methoxy}phenyl]methyl]-3,5-dioxo-1,2,4-oxadiazolidin-4-ide} tetrahydrate), an agonist of free fatty acid receptor","authors":"Chih-Ju Chou ,&nbsp;Chi-Wai Cheung ,&nbsp;Chien-Ching Lee ,&nbsp;Sheng-Nan Wu ,&nbsp;Rasa Liutkeviciene ,&nbsp;Vita Rovite ,&nbsp;Edmund Cheung So","doi":"10.1016/j.neulet.2025.138222","DOIUrl":"10.1016/j.neulet.2025.138222","url":null,"abstract":"<div><div>AS2034178, an agonist of free fatty acid receptor-1 or G protein-coupled receptor 40, enhances pancreatic β-cell function. Its impact on ionic currents in excitable cells, particularly pituitary tumor (GH<sub>3</sub>) cells, was investigated. AS2034178 suppressed transient (<em>I</em><sub>Na(T)</sub>) and late (<em>I</em><sub>Na(L)</sub>) components of voltage-gated Na<sup>+</sup> current (<em>I</em><sub>Na</sub>) with IC<sub>50</sub> values of 29.8 and 5.3 µM, respectively. It did not alter current–voltage relationship but shifted steady-state inactivation curve of <em>I</em><sub>Na(T)</sub> leftward. AS2034178 also blocked persistent Na<sup>+</sup> current (<em>I</em><sub>Na(P)</sub>) activated by long-lasting ramp voltages, and subsequent application of deltamethrin or tefluthrin attenuated its suppression. The compound prolonged recovery of <em>I</em><sub>Na(P)</sub> inactivation, shifted its inactivation curve, and shortened time constant for <em>I</em><sub>N(P)</sub> decay. Additionally, AS2034178 suppressed delayed-rectifier K<sup>+</sup> current (<em>I</em><sub>K(DR)</sub>) with a dissociation constant of 6.23 µM. Docking studies suggested AS2034178′s ability to interact with amino acid residues in hNa<sub>V</sub>1.7 channels.(supplementary data). AS2034178′s effects on ionic currents (<em>I</em><sub>Na</sub> and <em>I</em><sub>K(DR)</sub>) contribute to its mechanisms of action in culture or <em>in vivo</em>.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138222"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
VIP and PACAP enhance hippocampal neuronal cell proliferation especially GFAP-positive astrocytes, while PACAP inhibits neurite outgrowth VIP和PACAP促进海马神经元细胞的增殖,尤其是gap阳性星形胶质细胞的增殖,而PACAP抑制神经突的生长。
IF 2.5 4区 医学
Neuroscience Letters Pub Date : 2025-03-29 DOI: 10.1016/j.neulet.2025.138230
Barbora Bodorova , Denisa Mihalj , Tomas Havranek , Zuzana Bacova , Jan Bakos
{"title":"VIP and PACAP enhance hippocampal neuronal cell proliferation especially GFAP-positive astrocytes, while PACAP inhibits neurite outgrowth","authors":"Barbora Bodorova ,&nbsp;Denisa Mihalj ,&nbsp;Tomas Havranek ,&nbsp;Zuzana Bacova ,&nbsp;Jan Bakos","doi":"10.1016/j.neulet.2025.138230","DOIUrl":"10.1016/j.neulet.2025.138230","url":null,"abstract":"<div><div>Despite their known roles in regulating food intake, appetite, satiety, and social behavior, the roles of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in hippocampal neuronal cell development remain unclear. Therefore, the aim was to evaluate the effect of VIP and PACAP on 1) the proliferation of a hippocampal cell line, 2) the number of neurons and astrocytes in primary hippocampal cell culture, and 3) the morphology of primary hippocampal neurons. It was found that both VIP (100 nM) and PACAP (100 nM) stimulated the proliferation of E2 hippocampal cells over a 72-hour period. A significant increase in the number of NeuN-positive primary hippocampal neurons was observed following VIP incubation on day in vitro (DIV) 9. An increase in GFAP-positive cells following PACAP incubation was observed from DIV3 compared to DIV5, DIV7, and DIV9. PACAP significantly inhibited the growth of short neurites in primary hippocampal neurons. In conclusion, this study demonstrates that both neuropeptides VIP and PACAP influence the proliferation and growth of hippocampal neuronal cells, with PACAP having a more pronounced effect on astrocyte numbers and reducing neurite branching. These findings emphasize the role of VIP and PACAP in the hippocampus during early brain development.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"855 ","pages":"Article 138230"},"PeriodicalIF":2.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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