Neuroscience Letters最新文献

Abscisic acid ameliorates cognitive deficits in an amyloid-β-induced mouse model of Alzheimer's disease associated with alterations in markers of neuroplasticity and neuroinflammation. 脱落酸改善淀粉样蛋白β诱导的阿尔茨海默病小鼠模型中与神经可塑性和神经炎症标志物改变相关的认知缺陷。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-05-05 DOI: 10.1016/j.neulet.2026.138619

Fatemeh Shahsavari, Mohammad Amin Rajizadeh, Zeynab Pirmoradi, Mansoureh Sabzalizadeh, Kristi A Kohlmeier, Monavareh Soti, Mohammad Shabani

{"title":"Abscisic acid ameliorates cognitive deficits in an amyloid-β-induced mouse model of Alzheimer's disease associated with alterations in markers of neuroplasticity and neuroinflammation.","authors":"Fatemeh Shahsavari, Mohammad Amin Rajizadeh, Zeynab Pirmoradi, Mansoureh Sabzalizadeh, Kristi A Kohlmeier, Monavareh Soti, Mohammad Shabani","doi":"10.1016/j.neulet.2026.138619","DOIUrl":"https://doi.org/10.1016/j.neulet.2026.138619","url":null,"abstract":"<p><p>Abscisic acid (ABA, C<sub>15</sub>H<sub>20</sub>O<sub>4</sub>), a mammalian hormone, exhibits neuroprotective and anti-inflammatory properties. This study aimed to investigate the effects of ABA on the hippocampal-dependent processes: anxiety-, depression-like behaviors and cognitive impairments as well as levels of factors involved in neuroplasticity and neuroinflammation in an amyloid-β (Aβ)-induced mouse model of Alzheimer's disease (AD). One week following intracerebroventricular (i.c.v.) injection of Aβ<sub>1-42</sub> in male mice, ABA was administered i.c.v. at doses of 10 or 15 µg/µl for 7 consecutive days. Behavioral assessments were conducted using the novel object recognition, open field, elevated plus maze, tail suspension, Morris water maze, and passive avoidance tests. Hippocampal gene expression levels of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor (NMDAR), and nuclear factor-κB (NF-κB) were evaluated using real-time PCR. ABA treatment significantly attenuated anxiety-like behaviors and improved spatial, avoidance and recognition memory deficits induced by Aβ<sub>1-42</sub> administration with more behavioral domains affected at the 15  µg/µl dose. ABA induced significant upregulation in the hippocampus of NMDAR and BDNF expression and marked suppression of NF-κB in the ABA (15 µg/µl)-treated Aβ group, which could have played a mechanistic role in improvements in behaviors controlled by this structure. Histological analysis demonstrated attenuation of neuronal degeneration and pyknosis in the hippocampal CA1 region following ABA intervention. Collectively, these findings suggest that ABA ameliorates anxiety-related behaviors and cognitive impairments in an experimental mouse model of AD, potentially through modulation of neuroinflammatory and neuroplasticity-related pathways.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138619"},"PeriodicalIF":2.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841021","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

Formalin-induced pain preferentially activates orexin neurons in male mice. 福尔马林引起的疼痛优先激活雄性小鼠的食欲素神经元。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-05-05 DOI: 10.1016/j.neulet.2026.138620

Sosuke Fukasawa, Shinsaku Mukae, Arisa Matsuo, Moeko Kanaya

{"title":"Formalin-induced pain preferentially activates orexin neurons in male mice.","authors":"Sosuke Fukasawa, Shinsaku Mukae, Arisa Matsuo, Moeko Kanaya","doi":"10.1016/j.neulet.2026.138620","DOIUrl":"https://doi.org/10.1016/j.neulet.2026.138620","url":null,"abstract":"<p><p>Sex differences are well-documented across many functions of the orexin system; however, whether such differences extend to pain processing has been examined far less thoroughly. Therefore, we investigated whether males and females differ in orexin system engagement during nociception, and whether any differences reflect structural organization or functional recruitment. Adult C57BL/6N mice of both sexes were used, with females tested during proestrus and metestrus. Formalin was injected into the hind paw, and c-Fos induction in lateral hypothalamic orexin neurons was quantified together with orexin A/B fiber density and orexin receptor OX1R/OX2R mRNA expression in the lumbar cord. Orexin A and B were fully colocalized, allowing orexin B to serve as a reliable marker. The total number of orexin-immunoreactive neurons did not differ between the sexes or across estrous stages, and spinal orexinergic innervation and OX1R/OX2R mRNA levels were comparable across groups. In contrast, formalin induced a significantly higher proportion of c-Fos-positive orexin neurons in males, indicating male-biased recruitment of orexin neurons during nociception, despite equivalent anatomical substrates. These findings suggest that sex differences in orexin involvement in nociception are not attributable to structural disparities in the number of orexin neurons, spinal projections, or receptor expression, but instead arise from sex- and context-dependent differences in the functional activation of orexin neurons in response to painful stimuli.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138620"},"PeriodicalIF":2.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840984","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

Autophagy activation by taurine alleviates prion-induced mitochondrial dysfunction and neurotoxicity 牛磺酸激活自噬可减轻朊病毒诱导的线粒体功能障碍和神经毒性。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-01-29 DOI: 10.1016/j.neulet.2026.138526

Seung-Ok Lee, You-Jin Lee

{"title":"Autophagy activation by taurine alleviates prion-induced mitochondrial dysfunction and neurotoxicity","authors":"Seung-Ok Lee, You-Jin Lee","doi":"10.1016/j.neulet.2026.138526","DOIUrl":"10.1016/j.neulet.2026.138526","url":null,"abstract":"<div><div>Taurine (2-aminoethanesulfonic acid) is a naturally abundant amino acid known to support mitochondrial stability and neuronal stress resistance; however, its role in prion peptide–induced neurotoxicity has not been established. Here, we investigated whether taurine protects neuronal cells from toxicity induced by the prion protein fragment PrP(106–126) and whether autophagic flux contributes to this effect. Using an in vitro neuroblastoma cell model, we found that taurine pretreatment restored autophagic flux, as reflected by increased LC3-II/LC3-I ratios and reduced p62 accumulation. Taurine also attenuated PrP(106–126)–induced loss of mitochondrial membrane potential and apoptotic cell death. Importantly, inhibition of autophagic degradation with chloroquine prevented these protective effects, supporting a causal role for autophagy. These findings suggest that taurine mitigates prion peptide–mediated mitochondrial dysfunction by restoring autophagic flux in neuronal cells. While limited to a single in vitro model, this study provides foundational evidence that taurine-mediated modulation of autophagy may represent a potential therapeutic avenue for protein misfolding–related neurodegenerative disorders.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"875 ","pages":"Article 138526"},"PeriodicalIF":2.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097206","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

Color modulation of motion aftereffect on optomotor response in zebrafish larvae 运动后效对斑马鱼幼鱼光运动反应的颜色调制。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-02-05 DOI: 10.1016/j.neulet.2026.138538

Zulvikar Syambani Ulhaq

{"title":"Color modulation of motion aftereffect on optomotor response in zebrafish larvae","authors":"Zulvikar Syambani Ulhaq","doi":"10.1016/j.neulet.2026.138538","DOIUrl":"10.1016/j.neulet.2026.138538","url":null,"abstract":"<div><div>Visual aftereffects are perceptual distortions that occur after prolonged exposure to a visual stimulus. We examined zebrafish larval behaviors in response to unidirectional or bidirectional grating movement in red, green, and blue during adaptation and test phases. At the end of the test, larvae were collected to assess cone photoreceptor expression Unidirectional motion adaptation induced robust, color-dependent MAEs, with the strongest effect under red stimuli, followed by green and blue. In contrast, bidirectional adaptation abolished MAEs across all colors. General locomotor activity decreased during test phases, with unidirectional adaptation maintaining higher activity than bidirectional, particularly under red stimuli. Importantly, qRT-PCR and immunostaining revealed no changes in cone photoreceptor markers, indicating that the observed behavioral modulation occurred independently of photoreceptor expression. Together, these findings demonstrate that color selectively modulates motion perception in zebrafish larvae, with red stimuli producing the strongest motion adaptation effects, while general locomotor activity and photoreceptor expression remain largely unaffected. These behavioral patterns may arise from higher-order neural processing rather than from changes at the level of photoreceptor composition.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"875 ","pages":"Article 138538"},"PeriodicalIF":2.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137734","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

Chronic alcohol consumption and abstinence disrupt cholinergic gene expression in the mesopontine tegmentum of alcohol-preferring iP rats 长期饮酒和戒酒破坏嗜酒大鼠中筋膜胆碱能基因的表达。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-02-06 DOI: 10.1016/j.neulet.2026.138539

Shivani P. Vaidya , Daisy L. Spark , Leigh C. Walker , Paulo Pinares-Garcia , Roberta G. Anversa , Andrew J. Lawrence

{"title":"Chronic alcohol consumption and abstinence disrupt cholinergic gene expression in the mesopontine tegmentum of alcohol-preferring iP rats","authors":"Shivani P. Vaidya , Daisy L. Spark , Leigh C. Walker , Paulo Pinares-Garcia , Roberta G. Anversa , Andrew J. Lawrence","doi":"10.1016/j.neulet.2026.138539","DOIUrl":"10.1016/j.neulet.2026.138539","url":null,"abstract":"<div><div>The mesopontine tegmentum (MPT), consisting of the pedunculopontine tegmentum (PPTg) and laterodorsal tegmentum (LDTg) regulates reward and aversion via direct projections to key regions including the striatum, substantia nigra, and ventral tegmental area. Chronic alcohol consumption followed by abstinence significantly downregulates the M<sub>4</sub> muscarinic receptor in the dorsolateral striatum. Since cholinergic projections from the mesopontine tegmentum (MPT) provide an external source of acetylcholine to this region, it is imperative to investigate how alcohol exposure and subsequent abstinence induce molecular alterations within the cholinergic system of the mesopontine tegmentum. In this study, we first characterised PPTg and LDTg projections to the dorsal striatum in alcohol-preferring iP rats, then assessed changes to cholinergic gene expression in the MPT following long-term voluntary alcohol consumption and abstinence. Using a combined retrograde tracing and immunofluorescence approach, we demonstrate that PPTg and LDTg provide direct, bilateral cholinergic innervation to both the dorsolateral and dorsomedial striatum, with less topographical specificity than previously reported in other strains. Following six months of intermittent alcohol access, RT-qPCR revealed a transient decrease in <em>Chrna7</em> expression in the LDTg that returned to baseline after 14 days abstinence, and a downregulation of <em>Chrm4</em> expression in the PPTg during abstinence. Together, these findings reveal that long-term voluntary alcohol consumption reconfigures mesopontine cholinergic signalling, which may contribute to the neurobiological underpinnings of AUD.</div></div><div><h3>Significance statement</h3><div>Long-term voluntary alcohol consumption reconfigures mesopontine cholinergic signalling, which may contribute to the neurobiological underpinnings of AUD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"875 ","pages":"Article 138539"},"PeriodicalIF":2.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143057","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

Effects of vestibular habituation training on synaptic plasticity in the medial prefrontal cortex of mice with motion sickness 前庭习惯化训练对晕动病小鼠内侧前额叶皮层突触可塑性的影响。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-01-27 DOI: 10.1016/j.neulet.2026.138524

Shu Fang , Ben Wang , Shi-Li Zhang , Hao Wu , Wei-Wei Guo , Li-Li Ren , Yan Wang , Shi-Ming Yang

{"title":"Effects of vestibular habituation training on synaptic plasticity in the medial prefrontal cortex of mice with motion sickness","authors":"Shu Fang , Ben Wang , Shi-Li Zhang , Hao Wu , Wei-Wei Guo , Li-Li Ren , Yan Wang , Shi-Ming Yang","doi":"10.1016/j.neulet.2026.138524","DOIUrl":"10.1016/j.neulet.2026.138524","url":null,"abstract":"<div><h3>Background</h3><div>Motion sickness (MS) is triggered by vestibular conflict, yet how vestibular habituation training (VHT) engages higher-order cortical circuits remains unclear.</div></div><div><h3>Objective</h3><div>To test whether VHT modulates medial prefrontal cortex (mPFC) activity and structural plasticity in a rotational MS model.</div></div><div><h3>Methods</h3><div>Male C57BL/6J mice were assigned to control (CON), motion sickness (MS), or vestibular habituation training (VHT) groups. MS was induced by a single 4-g session (four 1-min bouts; total 4 min), whereas VHT mice received 14 daily sessions (30 × 1-min bouts/day; total 30 min/day). Behavioral outcomes, core body temperature, c-Fos expression in the medial vestibular nucleus (MVN) and mPFC, and mPFC dendritic and spine morphology (Golgi–Cox) were assessed after the final exposure (MS: induction session; VHT: day-14 session).</div></div><div><h3>Results</h3><div>MS caused hypoactivity, impaired motor coordination, reduced sucrose preference, hypothermia, and increased c-Fos in the MVN and mPFC. After VHT, behavioral and autonomic measures returned to control-like levels. MVN c-Fos was reduced to a control-like range, whereas mPFC c-Fos was attenuated but remained above controls. Morphologically, MS increased dendritic length and complexity, reduced spine density, and did not alter spine width. VHT restored dendritic length and spine density, increased dendritic complexity further, and reduced spine width.</div></div><div><h3>Conclusion</h3><div>VHT is associated with reduced MS-related neural activation and a distinct pattern of mPFC dendritic and spine remodeling, supporting higher-order cortical plasticity during vestibular habituation.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"875 ","pages":"Article 138524"},"PeriodicalIF":2.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086690","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

Human microglia express anti-inflammatory ISG15 in response to Neisseria meningitidis 人小胶质细胞表达抗炎ISG15对脑膜炎奈瑟菌的反应

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-02-11 DOI: 10.1016/j.neulet.2026.138543

Andrew M. Dunphy, Krishna Majithia, Quinton A. Krueger, M. Brittany Johnson, Ian Marriott

{"title":"Human microglia express anti-inflammatory ISG15 in response to Neisseria meningitidis","authors":"Andrew M. Dunphy, Krishna Majithia, Quinton A. Krueger, M. Brittany Johnson, Ian Marriott","doi":"10.1016/j.neulet.2026.138543","DOIUrl":"10.1016/j.neulet.2026.138543","url":null,"abstract":"<div><div>Glial cells respond to the presence of bacteria by producing inflammatory mediators but these responses can result in damage to the central nervous system (CNS). However, glia can also produce immunosuppressive mediators that can serve to mitigate such effects. Here, we demonstrate that human microglial cells and, to a lesser extent, primary human astrocytes, can express and secrete interferon stimulated gene 15 (ISG15) in response to a clinically relevant CNS pathogen, <em>Neisseria meningitidis,</em> and ligands for Toll-like receptor 4 (TLR4) that include lipopolysaccharide and lipooligosaccharide derived from <em>N. meningitidis</em>. Exogenous ISG15 failed to elicit human neutrophil-like cell migration and induce or augment their inflammatory responses. Similarly, recombinant ISG15 application did not elicit inflammatory cytokine or chemokine production by either human microglial cells or astrocytes, and did not augment their responses to TLR stimulation or <em>N. meningitidis</em> infection. Rather, ISG15 treatment limited <em>N. meningitidis</em>-induced NF-κB activation and associated inflammatory cytokine production by these cells, perhaps via a non-canonical TLR-mediated pathway. These observations may be indictive of a novel negative feedback loop whereby the recognition of bacterial motifs precipitates ISG15 expression by resident microglia that subsequently mitigates further neuroinflammatory responses.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"875 ","pages":"Article 138543"},"PeriodicalIF":2.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191069","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

Neural basis of cognitive-perceptual and negative affect: the linking role of ventral anterior insula connectivity 认知知觉与负性情绪的神经基础：脑岛前部腹侧连通性的连接作用。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-02-06 DOI: 10.1016/j.neulet.2026.138537

Liyun Han , Xianrui Li , Yawen Zhang , Jinbao Chen , Jing Zhang , Jiang Qiu , Min Chen

{"title":"Neural basis of cognitive-perceptual and negative affect: the linking role of ventral anterior insula connectivity","authors":"Liyun Han , Xianrui Li , Yawen Zhang , Jinbao Chen , Jing Zhang , Jiang Qiu , Min Chen","doi":"10.1016/j.neulet.2026.138537","DOIUrl":"10.1016/j.neulet.2026.138537","url":null,"abstract":"<div><h3>Background</h3><div>Schizotypal personality (SP) is characterized by cognitive-perceptual disturbances, interpersonal difficulties, and disorganized behavior. We examined associations between SP traits and affect, and insula-centered neural mechanisms underlying this link.</div></div><div><h3>Methods</h3><div>One hundred sixty-one university students completed the Schizotypal Personality Questionnaire–Brief and the Positive and Negative Affect Schedule and underwent resting-state fMRI. Seed-based whole-brain functional connectivity (FC) analyses used bilateral ventral anterior, dorsal anterior, and posterior insula seeds. Pearson correlations and mediation analyses tested associations among SP traits, negative affect, and FC.</div></div><div><h3>Results</h3><div>Cognitive–perceptual traits correlated positively with negative affect (<em>r</em> = 0.36, <em>p</em> < 0.001). FC between the right inferior parietal lobule (IPL.R) and the left ventral anterior insula (vAI.L) was positively correlated with cognitive–perceptual traits (<em>r</em> = 0.33, <em>p</em> < 0.001), whereas FC between the right cerebellar Crus I and the vAI.L was negatively correlated (<em>r</em> = −0.37, <em>p</em> < 0.001). FC between the right ventral anterior insula (vAI.R) and the Left Calcarine Gyrus (CAL.L) was also negative (<em>r</em> = −0.30, <em>p</em> < 0.001). vAI.L–IPL.R FC partially mediated the cognitive–perceptual traits–negative affect association (indirect effect = 0.1883, 95% bootstrap CI [0.0246, 0.4022]).</div></div><div><h3>Conclusion</h3><div>vAI.L–IPL.R FC partially accounts for the link between cognitive–perceptual traits and negative affect, highlighting a potential neural pathway underlying affective vulnerability in SP.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"875 ","pages":"Article 138537"},"PeriodicalIF":2.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143059","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

Modulatory effects of GLT-1 enhancer, MC-100093, on neuroinflammatory factors in mesocorticolimbic brain regions of female P rats exposed chronically to ethanol GLT-1增强剂MC-100093对长期暴露于乙醇的雌性大鼠中皮质边缘脑区神经炎症因子的调节作用

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-01-28 DOI: 10.1016/j.neulet.2026.138525

Khokon Kanti Bhowmik , Ahmed Alotaibi , Magid Abou-Gharbia , Wayne Childers , Youssef Sari

{"title":"Modulatory effects of GLT-1 enhancer, MC-100093, on neuroinflammatory factors in mesocorticolimbic brain regions of female P rats exposed chronically to ethanol","authors":"Khokon Kanti Bhowmik , Ahmed Alotaibi , Magid Abou-Gharbia , Wayne Childers , Youssef Sari","doi":"10.1016/j.neulet.2026.138525","DOIUrl":"10.1016/j.neulet.2026.138525","url":null,"abstract":"<div><div>Chronic ethanol intake increases extracellular glutamate concentrations in important reward-related brain regions, including the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), ultimately resulting in oxidative stress and inflammation. Recent studies from our laboratory demonstrated that MC-100093, a synthetic beta-lactam lacking antibacterial properties and functioning as a GLT-1 modulator, decreased ethanol consumption. This study examined the impact of the GLT-1 modulator, MC-100093, on chronic ethanol consumption and neuroinflammation in specific subregions of the NAc (core and shell) and mPFC (Prelimbic, PL; and Infralimbic, IL) in female alcohol preferring rats in a dose-dependent manner. MC-100093 treatment decreased ethanol consumption at both doses (100 and 150 mg/kg, i.p.) following a five-week drinking paradigm. MC-100093 attenuated ethanol-induced increase of the pro-inflammatory cytokines HMGβ-1 and TNF-α expression across all investigated mesocorticolimbic brain regions. Moreover, MC-100093 treatment attenuated the ethanol-induced increase of RAGE expression in these brain regions at both doses. MC-100093 treatment decreased ethanol consumption, and this behavioral outcome correlated with a reduction in pro-inflammatory markers, indicating that MC-100093 may serve as a potential agent for mitigating the effects of chronic ethanol exposure associated with inflammation.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"875 ","pages":"Article 138525"},"PeriodicalIF":2.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093165","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

Characterization of calcium currents and their contributions to firing behaviour of primary motoneurons in developing zebrafish 发育中的斑马鱼钙电流的表征及其对初级运动神经元放电行为的贡献。

IF 2 4区医学

Neuroscience Letters Pub Date : 2026-03-26 Epub Date: 2026-01-19 DOI: 10.1016/j.neulet.2026.138522

Stephanie F. Gaudreau, Tuan V. Bui

{"title":"Characterization of calcium currents and their contributions to firing behaviour of primary motoneurons in developing zebrafish","authors":"Stephanie F. Gaudreau, Tuan V. Bui","doi":"10.1016/j.neulet.2026.138522","DOIUrl":"10.1016/j.neulet.2026.138522","url":null,"abstract":"<div><div>Calcium currents in vertebrate motoneurons undergo developmental changes as motoneurons mature and develop specialized functions. The rapid development of zebrafish presents a unique opportunity to link changes in calcium currents of motoneurons to changes in the rapid and stereotyped motor maturation of zebrafish. As swimming matures from crude, large amplitude body bends to refined, low amplitude tailbeats, the involvement of the primary motoneurons that innervate fast muscle becomes less prevalent. During this time, primary motoneuron innervation, dendritic arborization, and firing properties become refined. In this study, we aimed to characterize the presence and influence on firing behaviour of low-voltage and high-voltage activated calcium currents in primary motoneurons during early development, when primary motoneurons undergo functional maturation. Our whole-cell patch-clamp electrophysiology data in zebrafish aged 2 to 5 days post-fertilization (dpf) reveal unique characteristics of calcium currents in zebrafish primary motoneurons, such as the influence of L-type and N-type calcium currents on the regulation of repetitive firing at 3 and 5 dpf, the emergence of P/Q-type calcium currents that regulate repetitive firing as of 4 dpf, and the absence of post-inhibitory rebounds characteristic of T-type calcium currents. These findings highlight how precise changes in properties of ion currents can shape neuronal function during development.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"875 ","pages":"Article 138522"},"PeriodicalIF":2.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019079","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