Neuroscience Letters最新文献

{"title":"Facilitation of supplementary motor area activity modulates the sense of effort: a theta burst stimulation study","authors":"Taishi Okegawa ,&nbsp;Daiki Yamasaki ,&nbsp;Naotsugu Kaneko ,&nbsp;Kimitaka Nakazawa","doi":"10.1016/j.neulet.2025.138482","DOIUrl":"10.1016/j.neulet.2025.138482","url":null,"abstract":"<div><div>The sense of effort, defined as the phenomenological experience of invested physical resources in the task, is a critical component of motor control. The supplementary motor area (SMA) has been implicated in generating this sense, yet it remains unclear how modulating SMA activity affects unconscious motor output when individuals intend to exert the same level of effort. The present study aimed to investigate how inhibiting and facilitating SMA activity influences the subjective sense of effort and associated motor output.</div><div>Twelve healthy volunteers received both facilitatory and inhibitory theta burst transcranial magnetic stimulation (TBS) applied to the SMA. We assessed corticospinal excitability, submaximal effort force production in an index finger abduction task (at a subjective effort level of 35% without visual feedback), and force-matching performance before and after the TBS protocols.</div><div>Results showed that facilitatory TBS led to a significant reduction in the submaximal index finger abduction force, which was accompanied by decreased EMG activity. In contrast, inhibitory TBS did not produce significant changes in submaximal force. Importantly, TBS applied to the SMA did not significantly alter motor-evoked potentials, indicating that corticospinal excitability remained unchanged. These findings suggest that enhanced SMA activity increases the effort required to produce a given force. The underlying mechanism likely involves changes in efference copy signals, as the effect occurred without altering the corticospinal excitability. In addition, force-matching performance was improved at 30 min after facilitatory TBS applied to the SMA. This delayed behavioral improvement may suggest a time-dependent modulation of sensorimotor processing, possibly involving the SMA and posterior parietal cortex, although network-level mechanisms remain speculative.</div><div>This study provides causal evidence for the SMA’s role in processing effort-related signals and contributes to a growing understanding of the cortical mechanisms underlying the sense of effort.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"872 ","pages":"Article 138482"},"PeriodicalIF":2.0,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668463","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}

{"title":"Bovine lactoferrin-induced antinociception through 5-HT1A/1D receptors in formalin-induced tonic pain","authors":"Sergio Ernesto Ávila-Morales,&nbsp;Maria Elisa Drago-Serrano,&nbsp;Beatriz Godínez-Chaparro","doi":"10.1016/j.neulet.2025.138490","DOIUrl":"10.1016/j.neulet.2025.138490","url":null,"abstract":"<div><div>Bovine lactoferrin (bLF) is a multifunctional glycoprotein that displays modulatory effects on pain through pathways not fully known. Therefore, we determined the role of the serotonergic system as a potential mechanism underlying the antinociceptive effect of bLF on formalin-induced tonic nociception. The formalin test was used to assess the antinociceptive effect—pain-like behaviour (flinching) at 1 h. The bLF-induced antinociceptive effect was prevented by the intrathecal (3 µg/rat), but not the intraplantar (30 µg/rat) administration of methiothepin, a non-selective 5-hydroxytryptamine (5-HT) antagonist. Moreover, intrathecal administration of WAY-100635 (6 µg/rat; selective 5-HT_1A receptor antagonist) and BRL1555724 (4 µg/rat; selective 5-HT_1D receptor antagonist) prevented the bLF-induced antinociceptive effect. However, intrathecal administration of SB-224289 (5 µg/rat; selective 5-TH_1B receptor antagonist) and SB-699551 µg/rat; selective 5-TH_5A receptor antagonist) did not prevent the bLF-induced antinociceptive effect. The above finding suggests that bLF reduces acute nociception induced by formalin, and this antinociceptive effect is mediated, at least in part, by the serotonergic system, acting only at the spinal level and not at the peripheral level, via activation of central 5-HT_1A/1D serotonergic receptors.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"872 ","pages":"Article 138490"},"PeriodicalIF":2.0,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735169","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}

{"title":"Alcohol-induced neuropathy associated downregulation of Kv7 channels in primary nociceptors","authors":"Feyza Alyu Altinok ,&nbsp;Ilhem Dallali ,&nbsp;Ahmed Hasan ,&nbsp;Abderaouf Boubekka ,&nbsp;Elif Kaya Tilki ,&nbsp;Yusuf Ozturk","doi":"10.1016/j.neulet.2025.138461","DOIUrl":"10.1016/j.neulet.2025.138461","url":null,"abstract":"<div><div>Chronic alcohol consumption is a well-known risk factor for peripheral neuropathy, often presenting with thermal hyperalgesia and mechanical allodynia. While the involvement of dorsal root ganglia (DRG) neurons in alcohol-induced neuropathy (AIN) is recognized, the molecular mechanisms—particularly the role of Kv7-KCNQ potassium channel remains insufficiently understood. This research focused on evaluating the impact ofchronic alcohol exposure on Kv7 channel function and gene expression in DRG neurons, focusing on the KCNQ2 and KCNQ5 subunits.A rat model of AIN was established via oral gavage administration of 35 % ethanol (10 g/kg, twice daily) for 10 weeks. Pain hypersensitivity was evaluated using the electronic von Frey and Hargreaves tests. Quantitative real-time PCR was used to evaluate the mRNA expression of KCNQ2 and KCNQ5 channels. M−current (IM) density and neuronal excitability were assessed through whole-cell voltage-clamp and current-clamp recordings, respectively.Chronic ethanol exposure significantly reduced both mechanical and thermal thresholds, confirming the development of neuropathic pain. We observed a marked downregulation in the mRNA expression of KCNQ2 and KCNQ5 subunits, accompanied by a diminished M−current density within DRG neurons. These alterations were linked to increased neuronal excitability and heightened pain sensitivity in rats exposed to ethanol.These findings demonstrate that AIN is marked by a significant downregulation of KCNQ2 and KCNQ5 channel expression and function, contributing to elevated neuronal excitability and the onset of thermal hyperalgesia and mechanical allodynia. The suppressed activity of KCNQ/M channels within DRG neurons of AIN rats highlights Kv7 channels as promising molecular targets for AIN therapy.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138461"},"PeriodicalIF":2.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564566","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}

{"title":"Involvement of substance P/NK1 receptor system in central sensitization in chronic pain","authors":"Juan Chen ,&nbsp;Yimin Lai ,&nbsp;Wei Li","doi":"10.1016/j.neulet.2025.138464","DOIUrl":"10.1016/j.neulet.2025.138464","url":null,"abstract":"<div><div>Chronic pain has become a serious health issue, affecting more than 30% of people worldwide. One of the main mechanisms of chronic pain is central sensitization. It is well known that substance P (SP) and its receptor, Neurokinin 1 receptor (NK1R), play an important role in transmission of nociceptive signals. However, whether SP/NK1R system is involved in central sensitization in chronic pain remains controversial. In the present study, we adopted spared nerve injury (SNI) mouse model to induce neuropathic pain and assessed the role of SP/NK1R system in the development of hyperalgesia and central sensitization. We observed that hyperalgesia occurred in non-injured body part of SNI mice in tail withdrawal test. We also demonstrated hyperexcitability of S1 apical dendrites in SNI mice. Notably, the hyperalgesia behavior and hyperactivity of S1 apical dendrites were alleviated by NK1R antagonist L-703606. These results indicate that SP/NK1R system is involved in central sensitization in chronic pain.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138464"},"PeriodicalIF":2.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597093","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}

{"title":"Short-term immobilization impairs pointing direction programming and early motor control processes","authors":"C.R. Scotto,&nbsp;F.R. Danion,&nbsp;Y. Blandin,&nbsp;L. Toussaint","doi":"10.1016/j.neulet.2025.138446","DOIUrl":"10.1016/j.neulet.2025.138446","url":null,"abstract":"<div><div>Short-term limb immobilization is a valuable method for studying the contribution of proprioception since it temporarily reduces sensory and motor inputs. While several studies have shown that immobilization impairs cognitive and sensorimotor processes, none have yet demonstrated how it could specifically impact the programming of movement <em>direction</em>. Here, participants (N = 32) made uncorrected pointing movements toward five visual targets located in different directions − but requiring constant amplitude − without benefiting from any visual feedback on the hand. Pointing was performed on two consecutive days by <em>Control</em> and <em>Immobilized</em> participants, the latter of whom had worn a splint on the right arm during this 24 h period. Results showed that immobilization increased the duration of movement planning (i.e., longer reaction time) necessary to specify hand-path direction. A greater counterclockwise directional bias was observed at peak acceleration in the <em>Immobilized</em> group and persisted until the uncorrected movement offset. These results suggest that immobilization impacts <em>direction</em> programming as well as early motor control processes. We argue that proprioception deprivation impairs the perception of limb position, leading to both slower and less accurate motor command selection. Overall, we interpret that the lack of proprioceptive feedback and efference copies may influence the accuracy of movement planning after 24 h of immobilization, possibly reflecting changes in processes related to internal model mechanisms.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138446"},"PeriodicalIF":2.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513406","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}

{"title":"TEMPOL alleviated tau pathology and cognitive deficits induced by P301S-tau","authors":"Xiao Li ,&nbsp;Ruijuan Liu ,&nbsp;Ye He ,&nbsp;Xifei Yang ,&nbsp;Ting Li ,&nbsp;Yan Feng","doi":"10.1016/j.neulet.2025.138465","DOIUrl":"10.1016/j.neulet.2025.138465","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most frequent of neurodegenerative disease affecting elderly people. However, there is still no curative therapeutic strategies in clinical practice. Here, we studied whether TEMPOL as a free radical scavenger can prevent memory deficits in P301S-tau mice. We found that TEMPOL administration markedly restored learning and memory impairments inducing by P301S-tau. We showed that TEMPOL had a potent capacity of inhibiting the expression of tau protein and its phosphorylation levels. The inflammatory response and synaptic defects induced by P301S-tau was also obviously improved TEMPOL treatment. Furthermore, proteomics showed 121 reversed proteins by TEMPOL treatment were primarily involved in immune system processes, innate immune responses, inflammatory responses, autophagosome assembly, lysosome organization, and autophagy. Taken together, TEMPOL played a critical role in P301S-tau-related cognitive impairments. These findings demonstrate that TEMPOL shows promise as a multi-target therapeutic agent for AD by modulating critical pathways implicated in its pathogenesis.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138465"},"PeriodicalIF":2.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597021","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}

{"title":"Transcutaneous auricular vagus nerve stimulation promotes post-spinal cord injury remyelination via α7nAChR-mediated activation of oligodendrocyte precursor cells","authors":"Lingxia Min ,&nbsp;Cheng Cheng ,&nbsp;Jiafei Chen ,&nbsp;Chao Ma ,&nbsp;Jilan Wang ,&nbsp;Mingliang Tan ,&nbsp;Ran Ran ,&nbsp;Xiaoyu Wu ,&nbsp;Rubing Yan ,&nbsp;Jingming Hou ,&nbsp;Hongliang Liu ,&nbsp;Zhou Feng","doi":"10.1016/j.neulet.2025.138466","DOIUrl":"10.1016/j.neulet.2025.138466","url":null,"abstract":"<div><div>Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique with emerging therapeutic potential for various central nervous system diseases. However, its therapeutic effects and mechanisms in spinal cord injury (SCI) remain largely unexplored. In this study, we demonstrated that ta-VNS significantly improved motor function recovery in SCI patients. Diffusion tensor imaging (DTI) further indicated that ta-VNS promoted structural repair of injured axons and myelin sheaths. Using a rodent model of SCI, we found that ta-VNS facilitated remyelination, attenuated tissue damage, and enhanced motor function recovery. Mechanistically, ta-VNS upregulated the expression of the α7 nicotinic acetylcholine receptor (α7nAChR) in oligodendrocyte precursor cells (OPCs), promoting their proliferation and differentiation into mature oligodendrocytes, thereby supporting remyelination. These beneficial effects of ta-VNS were abolished by administration of a selective α7nAChR antagonist. This study identifies the α7nAChR-mediated pro-myelination axis as a novel mechanistic basis for ta-VNS therapy, thereby establishing this non-invasive neuromodulation as a compelling strategy for promoting repair and recovery after SCI.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138466"},"PeriodicalIF":2.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145636833","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}

{"title":"Involvement of the right inferior parietal lobule network in ipsilateral spatial attention","authors":"Marino Iwakiri ,&nbsp;Yuhi Takeo ,&nbsp;Takashi Ikeda ,&nbsp;Masayuki Hara ,&nbsp;Hisato Sugata","doi":"10.1016/j.neulet.2025.138463","DOIUrl":"10.1016/j.neulet.2025.138463","url":null,"abstract":"<div><div>Unilateral spatial neglect (USN) significantly impairs mobility in patients following a stroke. The amount and quality of evidence supporting effective treatments for USN is still limited, primarily due to the unclear nature of its underlying neural mechanisms. As lesions in USN are not localized to a specific brain region, research has underscored the importance of evaluating USN from a network-based perspective. Nevertheless, the key functional regions at the core of this network are yet to be identified. Previously, we reported that the right inferior parietal lobule (IPL) may serve as the central hub in the neural network associated with USN. Therefore, this study aimed to determine the brain network centered on the right IPL by conducting seed-based functional connectivity analysis. Our results may contribute to a better understanding of the neural mechanisms in USN.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138463"},"PeriodicalIF":2.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582487","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}

{"title":"Everolimus ameliorates cognitive deficits and synaptic dysfunction in mice with prefrontal cortical ADNP knockdown","authors":"Yu Xiang ,&nbsp;Zeyu Zhang ,&nbsp;Yunrui Jiang ,&nbsp;Hongen Wei","doi":"10.1016/j.neulet.2025.138460","DOIUrl":"10.1016/j.neulet.2025.138460","url":null,"abstract":"<div><div>Activity-dependent neuroprotective protein (ADNP), a major risk gene for autism spectrum disorder (ASD) and intellectual disability (ID), is critical for brain development and cognition. Among its regulated processes, autophagy is notably affected, with mTORC1 overactivation acting as a negative regulator and frequently reported in ASD. Rapamycin can rescue ASD-related behaviors, and everolimus (EVR), an optimized derivative, is widely applied in clinical practice. However, its role in ADNP-related pathology remains unknown. Here, we established a prefrontal cortex (PFC) ADNP knockdown (KD) mouse model to examine behavioral and molecular consequences, and whether EVR provides benefit. We found that ADNP KD resulted in mTORC1 pathway activation, autophagy impairment, learning and memory deficits, and anxiety-like behaviors, concurrent with dysregulation of microtubule and synaptic proteins. Daily intraperitoneal EVR (5 mg/kg) can effectively alleviate the behavioral and molecular phenotypes caused by ADNP deficiency in the PFC, thereby establishing a strong rationale for targeting the mTOR pathway in treating ADNP-related cognitive impairments.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138460"},"PeriodicalIF":2.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564585","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}

{"title":"Piracetam reverses scopolamine-induced memory disorder in mice: an animal model using behavioral, oxidative, and cholinesterase biomarkers","authors":"Valfran da Silva Lima ,&nbsp;Guilherme Luz Emerick ,&nbsp;Valéria Dornelles Gindri Sinhorin ,&nbsp;Ritane Rose da Silva Lima ,&nbsp;Helidi Schaiane da Silva ,&nbsp;Kaiany Fernanda da Silva ,&nbsp;Antônio Carlos Alves de Sousa ,&nbsp;Francielly Rieger Silveira ,&nbsp;Amanda Lika Mizuno Saito ,&nbsp;Evelyn Lezzo Estevam ,&nbsp;Márcia Queiroz Latorraca","doi":"10.1016/j.neulet.2025.138462","DOIUrl":"10.1016/j.neulet.2025.138462","url":null,"abstract":"<div><div>Memory impairment diseases have become a serious health problem worldwide. In this context, an animal model capable of recognizing substances with the ability to recover memory disorders would be welcome. Thus, the present work aims to evaluate the effect of piracetam on reversal of scopolamine-induced memory deficit in male Swiss mice (n = 6) after fifteen days of treatment. To achieve this objective, behavioral, oxidative and cholinesterase inhibition markers were used. Memory impairment was evaluated by object and social recognition and step-down inhibitory avoidance tests. The evaluation of the redox state included superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase, thiobarbituric acid reactive substances, carbonyl proteins, ascorbic acid, and reduced glutathione. Scopolamine caused cognitive deficit, evidenced by the reduction in latency period and in the discrimination index (DI) of aversive, social, and declarative memories. However, piracetam significantly reversed those deficits. Scopolamine has increased the levels of thiobarbituric acid reactive substances. Scopolamine inhibited significantly brain and plasma cholinesterase activity. In conclusion, scopolamine at a dose of 0.8 mg/kg for 15 days induced memory deficit, oxidative damage and cholinesterase inhibition in brain of mice. Furthermore, piracetam at a dose of 200 mg/kg could reverse the memory impairment induced by scopolamine by mechanisms that are independent of the antioxidant action and cholinesterase inhibition. The present model has showed great sensibility and could be used to evaluate other drugs with the potential for the treatment of diseases related to memory damage.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"871 ","pages":"Article 138462"},"PeriodicalIF":2.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573866","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}