Neuroscience Letters最新文献

Repeated ketamine administration induces cross-tolerance to sodium salicylate but not to morphine in male rats. 反复给氯胺酮可诱导雄性大鼠对水杨酸钠的交叉耐受，但对吗啡无交叉耐受。

IF 2.2 4区医学

Neuroscience Letters Pub Date : 2026-10-20 DOI: 10.1016/j.neulet.2026.138766

Maryam Moghimian, Alireza Fathi, Amirhossein Ebadi, Sajjad Mansouri, Negar Shafaei-Bajestani, Seyd-Hosein Abtahi-Evari, Masoumeh Gholami

{"title":"Repeated ketamine administration induces cross-tolerance to sodium salicylate but not to morphine in male rats.","authors":"Maryam Moghimian, Alireza Fathi, Amirhossein Ebadi, Sajjad Mansouri, Negar Shafaei-Bajestani, Seyd-Hosein Abtahi-Evari, Masoumeh Gholami","doi":"10.1016/j.neulet.2026.138766","DOIUrl":"https://doi.org/10.1016/j.neulet.2026.138766","url":null,"abstract":"<p><p>Cross-tolerance profiles provide critical insights into shared neurobiological substrates among analgesics. This study evaluated whether repeated sub-anesthetic ketamine administration induces cross-tolerance to morphine or sodium salicylate. Thirty-six adults male Wistar rats (180-200 g, n = 6/group) received either normal saline or ketamine (10 mg/kg, i.p.) once daily for 8 consecutive days. Antinociceptive thresholds were assessed daily using the hot-plate test (52 ± 0.5 °C) at 45 min post-injection and expressed as the percentage of maximum possible effect (MPE%). On day 9, acute cross-tolerance challenges were conducted using morphine (10 mg/kg, i.p.) or sodium salicylate (300 mg/kg, i.p.). Serum malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity was measured on day 8 to evaluate systemic oxidative status. Repeated ketamine administration produced a progressive decline in MPE%, demonstrating marked antinociceptive tolerance by day 8. On day 9, morphine maintained full antinociceptive efficacy in ketamine-pretreated rats, indicating no cross-tolerance. Conversely, sodium salicylate-induced antinociception was significantly blunted, confirming cross-tolerance. Biochemically, ketamine pre-treatment did not elevate serum MDA and preserved SOD activity substantially better than morphine. In conclusion, repeated sub-anesthetic ketamine administration induces antinociceptive tolerance and selective cross-tolerance to sodium salicylate, while sparing morphine responsiveness. These behavioral adaptations parallel a favorable redox balance, highlighting distinct pharmacodynamic mechanisms governing ketamine interactions with opioid versus non-opioid regimens.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138766"},"PeriodicalIF":2.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228422","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

Endpoint-specific interactions between aerobic exercise and benfotiamine in chronic noise-induced prefrontal cortical dysfunction in mice. 有氧运动和苯福胺在慢性噪声诱导的小鼠前额皮质功能障碍中的终点特异性相互作用。

IF 2.2 4区医学

Neuroscience Letters Pub Date : 2026-10-19 DOI: 10.1016/j.neulet.2026.138765

Hadiseh Abdi Ziari, Fatemeh Shaki, Mohammad Seyedabadi, Alireza Safarzade, Fereshteh Talebpour Amiri

{"title":"Endpoint-specific interactions between aerobic exercise and benfotiamine in chronic noise-induced prefrontal cortical dysfunction in mice.","authors":"Hadiseh Abdi Ziari, Fatemeh Shaki, Mohammad Seyedabadi, Alireza Safarzade, Fereshteh Talebpour Amiri","doi":"10.1016/j.neulet.2026.138765","DOIUrl":"https://doi.org/10.1016/j.neulet.2026.138765","url":null,"abstract":"<p><p>Chronic environmental noise can impair brain redox and inflammatory homeostasis, but the effects of combined non-pharmacological and metabolic interventions remain unclear. This study investigated whether aerobic exercise and benfotiamine, separately or combined, attenuate noise-induced behavioral dysfunction and prefrontal cortical injury-related changes. Male Swiss albino mice were assigned to Control, Noise, Noise + aerobic exercise, Noise + benfotiamine (200 mg/kg/day), Noise + aerobic exercise + benfotiamine, or Noise + N-acetylcysteine (500 mg/kg/day) groups (n = 9/group). Noise-exposed mice received broadband industrial noise at 90 dB sound pressure level for 4 h/day for 28 days. Behavioral despair-like phenotypes, cortical redox status, inflammatory gene expression, and histopathology were evaluated. Noise increased immobility in the forced swim and tail suspension tests, elevated reactive oxygen species, nitric oxide, malondialdehyde, protein carbonyls, and pro-inflammatory transcripts, and reduced glutathione and antioxidant capacity. Both interventions attenuated multiple abnormalities. Aerobic exercise produced prominent behavioral effects and increased interleukin-10 expression, whereas benfotiamine strongly reduced reactive oxygen species, lipid peroxidation, and interleukin-1β. Significant exercise × benfotiamine interactions occurred for both behavioral tests, reactive oxygen species, tumor necrosis factor-α, interleukin-1β, and interleukin-10, but not for several other endpoints. The combined intervention frequently produced the most favorable absolute values, although significant interactions were generally subadditive rather than synergistic. Aerobic exercise and benfotiamine therefore provide broad but endpoint-specific protection against chronic noise-associated prefrontal cortical dysfunction.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138765"},"PeriodicalIF":2.2,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224686","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

Neuroprotective potential of safinamide against LPS-induced neuroinflammation and cognitive dysfunction in mice. 沙非胺对lps诱导的小鼠神经炎症和认知功能障碍的神经保护作用。

IF 2.2 4区医学

Neuroscience Letters Pub Date : 2026-10-17 DOI: 10.1016/j.neulet.2026.138763

Radha Kasaraneni, Prasada Chowdari Gurram, Shampreeth Sai Narne, M A Muawia Babiker, Adam Salah, Narayanarao Alla, Alex Rebello

{"title":"Neuroprotective potential of safinamide against LPS-induced neuroinflammation and cognitive dysfunction in mice.","authors":"Radha Kasaraneni, Prasada Chowdari Gurram, Shampreeth Sai Narne, M A Muawia Babiker, Adam Salah, Narayanarao Alla, Alex Rebello","doi":"10.1016/j.neulet.2026.138763","DOIUrl":"10.1016/j.neulet.2026.138763","url":null,"abstract":"<p><p>Neuroinflammation, a key pathological hallmark of neurological diseases, contributes to neurodegeneration, synaptic dysfunction, and cognitive decline. Safinamide shows toll-like receptor-mediated anti-inflammatory effects in cellular models; however, it's in vivo neuroprotective and neuroinflammatory effects remain unexplored. In the present investigation, the anti-neuroinflammatory impact of safinamide was evaluated in lipopolysaccharide (LPS)-induced mice using behavioral, biochemical, and histopathological assessments. LPS was administered intraperitoneally from days 8 to 15 to induce neuroinflammation, followed by 15 days of safinamide treatment at 10 mg/kg and 20 mg/kg. Safinamide 20 mg/kg significantly improved spatial and recognition memory, as evidenced by the percentage alternation in the Y-maze and recognition index in the novel object recognition test. Furthermore, safinamide significantly reduced the levels of Toll-like receptor 4 (TLR4), phosphorylated NF-κB (p-NF-κB), NLRP3, TNF-α, IL-6, IL-1β, acetylcholinesterase (AChE), and malondialdehyde (MDA), and increased levels of glutathione (GSH), catalase, and superoxide dismutase (SOD). Histopathological analysis revealed decreased amyloid-β deposition and preservation of neuronal architecture. These findings suggest that safinamide modulates neuroinflammatory and oxidative stress pathways and exhibits promising neuroprotective potential against inflammation-associated cognitive impairment.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138763"},"PeriodicalIF":2.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207299","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

Sivelestat sodium improves post-resuscitation brain outcomes possibly by inhibiting cell pyroptosis via inactivating the cGAS/STING/TBK1 pathway. 西维司他钠改善复苏后脑预后可能是通过灭活cGAS/STING/TBK1途径抑制细胞焦亡。

IF 2.2 4区医学

Neuroscience Letters Pub Date : 2026-10-17 DOI: 10.1016/j.neulet.2026.138764

Pan Ying, Tengda Zhou, Yufeng Hu, Yujie Luo, Jiefeng Xu, Xianlong Wu

{"title":"Sivelestat sodium improves post-resuscitation brain outcomes possibly by inhibiting cell pyroptosis via inactivating the cGAS/STING/TBK1 pathway.","authors":"Pan Ying, Tengda Zhou, Yufeng Hu, Yujie Luo, Jiefeng Xu, Xianlong Wu","doi":"10.1016/j.neulet.2026.138764","DOIUrl":"10.1016/j.neulet.2026.138764","url":null,"abstract":"<p><p>Sivelestat sodium (SS) is shown to protect vital organs against regional ischemic stimuli. We investigated its effects on brain outcomes after global ischemic stimuli resulted from cardiac arrest (CA) and resuscitation. Adult pigs were randomly divided into sham (S), cardiopulmonary resuscitation (CPR), and CPR + SS groups. The animals were subjected to 9 mins of CA followed by 6 mins of CPR. After resuscitation, a dose of 10 mg/kg of SS was intravenously administered for 60 mins. Post-resuscitation brain injury and neurological function were regularly evaluated. Brain hippocampus tissues were harvested to measure histopathological injury, cell apoptosis, pyroptosis-related proteins and proinflammatory cytokines, and the cGAS/STING/TBK1 pathway. Consequently, post-resuscitation brain injury and neurological dysfunction were observed in those animals experiencing the CA/CPR procedure. However, they were significantly milder in the CPR + SS group than in the CPR group. Hippocampal histopathological injury and apoptosis were observed after resuscitation in the CPR and CPR + SS groups. Nevertheless, SS treatment significantly decreased both of them compared with the CPR group. Furthermore, pyroptosis-related proteins were upregulated, its-related proinflammatory cytokines were increased, and the cGAS/STING/TBK1 pathway was activated in post-resuscitation hippocampus in the CPR and CPR + SS groups. Likewise, SS treatment significantly reversed the changes of pyroptosis-related proteins and proinflammatory cytokines, and the cGAS/STING/TBK1 pathway compared to the CPR group. Thus, SS treatment was effective in improving post-resuscitation brain outcomes, and its protective role was possibly related to the inhibition of cell pyroptosis through the inactivation of the cGAS/STING/TBK1 pathway.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138764"},"PeriodicalIF":2.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207270","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

Loss of APOBEC1 disrupts RNA editing homeostasis and accelerates prion disease progression. APOBEC1的缺失破坏RNA编辑稳态并加速朊病毒疾病进展。

IF 2.2 4区医学

Neuroscience Letters Pub Date : 2026-10-14 DOI: 10.1016/j.neulet.2026.138762

Korina Karagianni, Eirini Kanata, Eleni Kovatsi, Spyros Pettas, Mantiana Topouzi, Konstantinos Xanthopoulos, Theodoros Sklaviadis, Dimitra Dafou

{"title":"Loss of APOBEC1 disrupts RNA editing homeostasis and accelerates prion disease progression.","authors":"Korina Karagianni, Eirini Kanata, Eleni Kovatsi, Spyros Pettas, Mantiana Topouzi, Konstantinos Xanthopoulos, Theodoros Sklaviadis, Dimitra Dafou","doi":"10.1016/j.neulet.2026.138762","DOIUrl":"https://doi.org/10.1016/j.neulet.2026.138762","url":null,"abstract":"<p><strong>Background: </strong>RNA editing is an epitranscriptomic mechanism that shapes transcriptome diversity and fine-tunes neuronal function. While adenosine-to-inosine (A-to-I) editing by ADAR enzymes has been extensively studied in neurodegenerative disorders, the role of cytidine-to-uridine (C-to-U) editing catalyzed by APOBEC1 remains largely unexplored.</p><p><strong>Methods: </strong>We investigated the impact of APOBEC1 on RNA editing homeostasis and prion disease progression using complementary in vitro and in vivo models. Global RNA editing and gene expression profiles were established in non-infected N2A and prion-infected sc-N2A murine neuroblastoma cells, under control conditions or following APOBEC1 depletion. APOBEC1 was silenced by shRNA-mediated knockdown to assess its regulatory contribution. In vivo disease progression was assessed in Apobec1 knockout mice subjected to RML prion infection to evaluate survival outcomes.</p><p><strong>Results: </strong>Prion infection was associated with a global increase in RNA editing and an expanded repertoire of edited transcripts in sc-N2A cells. APOBEC1 depletion markedly reduced the overall editing levels, affecting both A-to-I and C-to-U editing events, reshaping editing patterns in transcripts associated with RNA and protein transport, cellular stress responses, synaptic signaling, and neuroimmune interactions. Consistently, Apobec1 KO mice exhibited accelerated body weight loss and significantly shortened survival following RML prion challenge.</p><p><strong>Conclusions: </strong>These findings support APOBEC1 as a contributor to RNA editing homeostasis and suggest that APOBEC1 loss reduces resilience to prion-induced neurodegenerative stress. APOBEC1 deficiency was associated with altered editome profiles in prion-infected cells and accelerated disease progression in the RML prion model.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138762"},"PeriodicalIF":2.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183497","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

Mechanistic insights into Aβ effects on neural stem cell proliferation and differentiation. Aβ对神经干细胞增殖和分化的作用机制。

IF 2.2 4区医学

Neuroscience Letters Pub Date : 2026-09-26 DOI: 10.1016/j.neulet.2026.138745

Yixin Zhao, Ying Yang, Lingdi Zhang, Beibei Hu, Zhenjun Yang, Zhihong Chen

{"title":"Mechanistic insights into Aβ effects on neural stem cell proliferation and differentiation.","authors":"Yixin Zhao, Ying Yang, Lingdi Zhang, Beibei Hu, Zhenjun Yang, Zhihong Chen","doi":"10.1016/j.neulet.2026.138745","DOIUrl":"10.1016/j.neulet.2026.138745","url":null,"abstract":"<p><p>Amyloid-β (Aβ) accumulation impairs hippocampal neural stem cell (NSC) function, but whether Aβ biases NSC lineage commitment toward the astrocytic lineage remains unclear. In this study, primary hippocampal NSCs from neonatal Sprague-Dawley rats were treated with 60 μM Aβ25-35 fragment, close to the 48-h half-maximal inhibitory concentration (IC<sub>50</sub> ≈ 57.8 μM) determined by a CCK-8 assay. After 48 h, the proportions of Nestin<sup>+</sup> and 5-ethynyl-2'-deoxyuridine (EdU)<sup>+</sup> cells were significantly decreased (P < 0.01 and P < 0.001, respectively). After 7 days of differentiation, the proportion of glial fibrillary acidic protein (GFAP)<sup>+</sup> cells was significantly increased (P < 0.001). GFAP<sup>+</sup> cells exhibited an increased number of processes but shortened process length. Western blotting confirmed decreased Nestin and increased GFAP protein levels (both P < 0.01). Network-based bioinformatics screening identified 124 overlapping genes between Aβ-related targets and NSC-associated genes, with the PI3K-Akt pathway most highly enriched; validation showed a reduced p-Akt/Akt ratio (P < 0.01), decreased p-GSK-3β (Ser9) and β-catenin levels (P < 0.001), and upregulated total GSK-3β (P < 0.05). Taken together, these findings indicate that Aβ25-35 inhibits NSC proliferation and promotes astrocytic lineage differentiation, at least partly through suppression of the PI3K/Akt/GSK-3β/β-catenin pathway.</p>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":" ","pages":"138745"},"PeriodicalIF":2.2,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063187","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

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

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