Neuroscience最新文献_第6页

EEG theta dynamics for error processing during online movement control 在线运动控制中误差处理的EEG θ动态。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-28 DOI: 10.1016/j.neuroscience.2025.12.065

Sarah Kessouri , Frederic R Danion , Jean-François Lepage , Pierre-Michel Bernier

To ensure optimal visuomotor feedback control during manual tracking, the brain must continuously monitor the error between the hand and the target. Modulations in the theta band (3–8 Hz) are related to error processing, but this has been mainly shown in cognitive control contexts. Hence, their relationship with hand-target errors during online control remains unclear. Here we assessed the impact of motor error processing on EEG theta-band activity in 29 healthy participants while they performed continuous tracking of a moving target with their dominant (right) hand. Two conditions were used to manipulate error processing demands: 1) in the Repeated condition, the same target trajectory was presented 80 times, allowing participants to implicitly learn the pattern and reduce tracking errors; 2) in the Random condition, 80 different trajectories were used, inducing persistent high tracking errors. Behavioral analyses confirmed that tracking errors were significantly higher in the Random than in the Repeated condition. Importantly, EEG theta power was also significantly higher in the Random condition, with a peak difference occurring at electrodes overlaying the left sensorimotor regions. This effect was selective to theta activity, as there was no modulation in alpha- (8–12 Hz) and beta-band (15–30 Hz) activity. Overall, this study extends the role of theta oscillations to online error processing in the context of motor control. It is possible that theta modulations reflected cortical activity mediating the communication and integration of information within sensorimotor circuits including the motor, premotor and parietal cortex, which are known to mediate online movement control.

在手动跟踪过程中，为了保证最佳的视觉运动反馈控制，大脑必须持续监测手与目标之间的误差。θ波段（3-8 Hz）的调制与错误处理有关，但这主要表现在认知控制环境中。因此，它们与在线控制中手靶误差的关系尚不清楚。在这里，我们评估了运动错误处理对29名健康参与者的脑电图θ波段活动的影响，当他们用左手（右手）连续跟踪运动目标时。实验采用两种条件来操纵错误处理需求：1)重复条件下，同一目标轨迹被呈现80次，使被试内隐学习模式，减少跟踪误差；2)在随机条件下，使用了80种不同的轨迹，导致持续的高跟踪误差。行为分析证实，随机条件下的跟踪误差明显高于重复条件。重要的是，随机条件下的EEG θ波功率也明显更高，在左侧感觉运动区域的电极上出现峰值差异。这种效应对θ活动是选择性的，因为α -（8-12 Hz）和β波段（15-30 Hz）活动没有调制。总的来说，本研究将θ振荡的作用扩展到运动控制中的在线错误处理。θ波调制可能反映了在感觉运动回路（包括运动、前运动和顶叶皮层）中介导信息交流和整合的皮质活动，这些回路已知介导在线运动控制。

{"title":"EEG theta dynamics for error processing during online movement control","authors":"Sarah Kessouri , Frederic R Danion , Jean-François Lepage , Pierre-Michel Bernier","doi":"10.1016/j.neuroscience.2025.12.065","DOIUrl":"10.1016/j.neuroscience.2025.12.065","url":null,"abstract":"<div><div>To ensure optimal visuomotor feedback control during manual tracking, the brain must continuously monitor the error between the hand and the target. Modulations in the theta band (3–8 Hz) are related to error processing, but this has been mainly shown in cognitive control contexts. Hence, their relationship with hand-target errors during online control remains unclear. Here we assessed the impact of motor error processing on EEG theta-band activity in 29 healthy participants while they performed continuous tracking of a moving target with their dominant (right) hand. Two conditions were used to manipulate error processing demands: 1) in the Repeated condition, the same target trajectory was presented 80 times, allowing participants to implicitly learn the pattern and reduce tracking errors; 2) in the Random condition, 80 different trajectories were used, inducing persistent high tracking errors. Behavioral analyses confirmed that tracking errors were significantly higher in the Random than in the Repeated condition. Importantly, EEG theta power was also significantly higher in the Random condition, with a peak difference occurring at electrodes overlaying the left sensorimotor regions. This effect was selective to theta activity, as there was no modulation in alpha- (8–12 Hz) and beta-band (15–30 Hz) activity. Overall, this study extends the role of theta oscillations to online error processing in the context of motor control. It is possible that theta modulations reflected cortical activity mediating the communication and integration of information within sensorimotor circuits including the motor, premotor and parietal cortex, which are known to mediate online movement control.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 280-289"},"PeriodicalIF":2.8,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Functional analysis of glucocorticoid treatment associated astrocyte-proteins 糖皮质激素治疗相关星形细胞蛋白的功能分析。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-28 DOI: 10.1016/j.neuroscience.2025.12.067

Chuin Hau Teo , Liau Ze Huai , Ishwar S. Parhar , Tomoko Soga

Stress induces various neurobiological changes related to neurodegenerative diseases or mental disorders, including elevated neuronal dysfunction, neurotransmitter degradation and turnover. Astrocytes regulate synapses bidirectionally as neuroprotective glia. While glucocorticoids are generally well studied, specific cellular mechanisms require further investigation. Neuronal dysfunction characterized by changes in glucocorticoid signaling is associated with changes in astrocytes; however, very little is known about the impact of glucocorticoids on astrocyte-specific cellular reactions. We have analyzed protein expression patterns following dexamethasone treatment of normal human astrocyte cultures. Protein analysis of cortical astrocyte cultures treated with dexamethasone for 48 h using LCMS/MS identified 3 unique proteins with ≥ twofold change in expression in the cell lysate and cell culture medium. Clustering analysis associated with these protein expression changes is known to be impacted by glucocorticoids. The upregulation of phosphoglycerate kinase and downregulation of pyruvate kinase strongly suggest a disrupted glycolytic process, which may hinder the astrocyte-neuron lactate shuttle critical for neuronal energy supply and cognitive function. Furthermore, the downregulation of insulin in the astrocyte culture medium indicates reduced insulin export from the astrocytes. These findings suggest that dexamethasone exposure has a pronounced effect on astrocyte metabolism and deploys astrocyte-specific patterns of regulatory responses to glucocorticoids and controls neuronal activation.

应激诱导与神经退行性疾病或精神障碍相关的各种神经生物学变化，包括神经元功能障碍升高、神经递质降解和转换。星形胶质细胞作为神经保护胶质双向调节突触。虽然糖皮质激素的研究普遍很好，但具体的细胞机制需要进一步研究。以糖皮质激素信号变化为特征的神经元功能障碍与星形胶质细胞的变化有关；然而，糖皮质激素对星形胶质细胞特异性细胞反应的影响知之甚少。我们分析了在地塞米松治疗后正常人类星形胶质细胞培养的蛋白表达模式。使用LCMS/MS对地塞米松作用48 h的皮质星形胶质细胞进行蛋白分析，鉴定出3个独特的蛋白，在细胞裂解液和细胞培养基中表达 ≥ 倍变化。已知与这些蛋白表达变化相关的聚类分析受到糖皮质激素的影响。磷酸甘油酸激酶的上调和丙酮酸激酶的下调强烈提示糖酵解过程中断，这可能阻碍星形胶质细胞-神经元乳酸穿梭，这对神经元能量供应和认知功能至关重要。此外，星形胶质细胞培养基中胰岛素的下调表明星形胶质细胞胰岛素输出减少。这些发现表明，地塞米松暴露对星形胶质细胞代谢有显著影响，并部署星形胶质细胞对糖皮质激素的特异性调节反应模式，并控制神经元激活。

{"title":"Functional analysis of glucocorticoid treatment associated astrocyte-proteins","authors":"Chuin Hau Teo , Liau Ze Huai , Ishwar S. Parhar , Tomoko Soga","doi":"10.1016/j.neuroscience.2025.12.067","DOIUrl":"10.1016/j.neuroscience.2025.12.067","url":null,"abstract":"<div><div>Stress induces various neurobiological changes related to neurodegenerative diseases or mental disorders, including elevated neuronal dysfunction, neurotransmitter degradation and turnover. Astrocytes regulate synapses bidirectionally as neuroprotective glia. While glucocorticoids are generally well studied, specific cellular mechanisms require further investigation. Neuronal dysfunction characterized by changes in glucocorticoid signaling is associated with changes in astrocytes; however, very little is known about the impact of glucocorticoids on astrocyte-specific cellular reactions. We have analyzed protein expression patterns following dexamethasone treatment of normal human astrocyte cultures. Protein analysis of cortical astrocyte cultures treated with dexamethasone for 48 h using LCMS/MS identified 3 unique proteins with ≥ twofold change in expression in the cell lysate and cell culture medium. Clustering analysis associated with these protein expression changes is known to be impacted by glucocorticoids. The upregulation of phosphoglycerate kinase and downregulation of pyruvate kinase strongly suggest a disrupted glycolytic process, which may hinder the astrocyte-neuron lactate shuttle critical for neuronal energy supply and cognitive function. Furthermore, the downregulation of insulin in the astrocyte culture medium indicates reduced insulin export from the astrocytes. These findings suggest that dexamethasone exposure has a pronounced effect on astrocyte metabolism and deploys astrocyte-specific patterns of regulatory responses to glucocorticoids and controls neuronal activation.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 50-58"},"PeriodicalIF":2.8,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Reduced EEG complexity in stable coronary artery disease: an evidence of covert brain dysfunction 稳定冠状动脉疾病脑电图复杂性降低：隐性脑功能障碍的证据

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-26 DOI: 10.1016/j.neuroscience.2025.12.061

Bixiu Huo , Bin Wang , Hongxiao Jia

Background

Accumulating evidence indicates that coronary heart disease (CHD) is frequently accompanied by cerebral injury. Non-linear electroencephalogram (EEG) analysis is an effective method for capturing abnormal EEG signal dynamics. This study characterized the complexity of EEG in CHD patients based on non-linear indices.

Methods

Twenty-seven patients with CHD were enrolled, as well as an equal number of non-coronary controls. Five-minute, resting-state EEG recordings were obtained under standardized conditions. Non-linear dynamics were quantified using Lempel–Ziv complexity (LZC), permutation Lempel–Ziv complexity (PLZC), sample entropy (SampEn), and permutation entropy (PE). Between-group differences were assessed by independent-samples t-tests. Within the CHD cohort, Pearson correlations were calculated between each non-linear index and clinical variables—age, disease duration, left-ventricular ejection fraction (LVEF %), and number of affected coronary arteries.

Results

Compared with controls, the CHD cohort exhibited significantly reduced LZC_mean, LZC_midp, SampEn, PLZC, and PE at multiple electrodes distributed across the entire scalp. A representative finding showed that: at electrode T8, LZC_mean was lower in CHD patients than in controls (0.73 ± 0.09 vs 0.79 ± 0.08; t = −2.683, p = 0.010). Age and disease duration were negatively correlated with several non-linear indices; for example, disease duration inversely predicted LZC_midp at FPz (r = −0.573, adjusted p = 0.004). LVEF% was positively associated with selected measures. No significant correlations were found between the number of affected coronary arteries and any EEG complexity metrics.

Conclusion

CHD patients demonstrated significantly lower total spectrum EEG complexity compared to non-CHD controls, offering novel electrophysiological evidence of central nervous system impairment in cardiovascular disease and suggesting potential functional brain alterations.

背景：越来越多的证据表明，冠心病（CHD）经常伴有脑损伤。非线性脑电图分析是捕捉异常脑电图动态信号的有效方法。本研究基于非线性指标表征冠心病患者脑电图的复杂性。方法：纳入27例冠心病患者，以及同等数量的非冠状动脉对照组。在标准化条件下获得5分钟静息状态脑电图记录。采用Lempel-Ziv复杂度（LZC）、置换Lempel-Ziv复杂度（PLZC）、样本熵（SampEn）和置换熵（PE）对非线性动力学进行量化。采用独立样本t检验评估组间差异。在冠心病队列中，计算每个非线性指数与临床变量（年龄、病程、左室射血分数（LVEF %）和受影响冠状动脉数量）之间的Pearson相关性。结果：与对照组相比，冠心病组在分布于整个头皮的多个电极上的LZCmean、LZCmidp、SampEn、PLZC和PE均显著降低。一项具有代表性的研究结果显示：在电极T8，冠心病患者的LZCmean低于对照组（0.73 ± 0.09 vs 0.79 ± 0.08;t = -2.683,p = 0.010）。年龄、病程与多个非线性指标呈负相关；例如，疾病持续时间与LZCmidp在FPz呈负相关（r = -0.573，调整后p = 0.004）。LVEF%与所选措施呈正相关。受影响的冠状动脉数目与脑电图复杂性指标之间无显著相关性。结论：与非冠心病对照组相比，冠心病患者脑电图总谱复杂性明显降低，为心血管疾病中枢神经系统损伤提供了新的电生理证据，提示潜在的脑功能改变。

{"title":"Reduced EEG complexity in stable coronary artery disease: an evidence of covert brain dysfunction","authors":"Bixiu Huo , Bin Wang , Hongxiao Jia","doi":"10.1016/j.neuroscience.2025.12.061","DOIUrl":"10.1016/j.neuroscience.2025.12.061","url":null,"abstract":"<div><h3>Background</h3><div>Accumulating evidence indicates that coronary heart disease (CHD) is frequently accompanied by cerebral injury. Non-linear electroencephalogram (EEG) analysis is an effective method for capturing abnormal EEG signal dynamics. This study characterized the complexity of EEG in CHD patients based on non-linear indices.</div></div><div><h3>Methods</h3><div>Twenty-seven patients with CHD were enrolled, as well as an equal number of non-coronary controls. Five-minute, resting-state EEG recordings were obtained under standardized conditions. Non-linear dynamics were quantified using Lempel–Ziv complexity (LZC), permutation Lempel–Ziv complexity (PLZC), sample entropy (SampEn), and permutation entropy (PE). Between-group differences were assessed by independent-samples t-tests. Within the CHD cohort, Pearson correlations were calculated between each non-linear index and clinical variables—age, disease duration, left-ventricular ejection fraction (LVEF %), and number of affected coronary arteries.</div></div><div><h3>Results</h3><div>Compared with controls, the CHD cohort exhibited significantly reduced LZC<sub>mean</sub>, LZC<sub>midp</sub>, SampEn, PLZC, and PE at multiple electrodes distributed across the entire scalp. A representative finding showed that: at electrode T8, LZC<sub>mean</sub> was lower in CHD patients than in controls (0.73 ± 0.09 vs 0.79 ± 0.08; t = −2.683, p = 0.010). Age and disease duration were negatively correlated with several non-linear indices; for example, disease duration inversely predicted LZC<sub>midp</sub> at FPz (r = −0.573, adjusted p = 0.004). LVEF% was positively associated with selected measures. No significant correlations were found between the number of affected coronary arteries and any EEG complexity metrics.</div></div><div><h3>Conclusion</h3><div>CHD patients demonstrated significantly lower total spectrum EEG complexity compared to non-CHD controls, offering novel electrophysiological evidence of central nervous system impairment in cardiovascular disease and suggesting potential functional brain alterations.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 229-240"},"PeriodicalIF":2.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Alterations in auditory midbrain processing is observed in both female and male mouse model of Fragile X Syndrome 在脆性 X 综合征的雌性和雄性小鼠模型中观察到听觉中脑加工的改变。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-25 DOI: 10.1016/j.neuroscience.2025.12.062

Abdullah Abdullah , Xiuping Liu , Kartikeya Murari , Jun Yan , Ning Cheng

Auditory hypersensitivity is a common phenotype in Fragile X Syndrome. Electrophysiology studies at the inferior colliculus of male FMR1-knockout (KO) mice previously demonstrated increased neuronal firing, suggesting that the inferior colliculus is involved in auditory hypersensitivity. Here, we further explored whether the central nucleus of the inferior colliculus (ICc) is involved in auditory hypersensitivity in both female and male KO mice. Tone-evoked in-vivo electrophysiology recordings from ICc neurons of anesthetized (ketamine/xylazine) KO mice at both postnatal day 20 (P20) and 30 (P30) demonstrated increased spikes compared to age- and sex-matched wild-type (WT) mice. Within the KO group, increased spikes were observed in females compared with male mice. Both female and male KO mice also displayed decreased minimum threshold and enhanced response duration at both ages. Additionally, female P30 KO mice displayed weaker inverse relationship between response latency and spike number compared to their WT counterparts. Regarding developmental changes, spike number decreased with maturation in both female and male KO mice. Response duration reduced with age in both sexes of both genotypes, while minimum threshold decreased in the male mice. Finally, we observed an age-related strengthening of the inverse relationship between response latency and magnitude only in the WT mice. Our findings indicate that the ICc display auditory processing deficits particularly in the female KO mice and in young animals highlighting the importance of including female subjects in future studies, and studying early development, which could be an ideal stage for interventions.

听觉过敏是脆性 X 综合征的常见表型。在雄性fmr1敲除（KO）小鼠的下丘的电生理学研究先前显示神经元放电增加，这表明下丘参与了听觉超敏反应。在这里，我们进一步探讨了下丘中央核（ICc）是否参与雌性和雄性KO小鼠的听觉超敏反应。在出生后20天（P20）和30天（P30）麻醉（氯胺酮/噻嗪）KO小鼠的ICc神经元的音调诱发的体内电生理记录显示，与年龄和性别匹配的野生型（WT）小鼠相比，峰值增加。在KO组中，与雄性小鼠相比，雌性小鼠的峰值增加。雌性和雄性KO小鼠在两个年龄段均表现出最小阈值降低和反应持续时间延长。此外，雌性P30 KO小鼠的反应潜伏期与脉冲数的反比关系较弱。在发育变化方面，雌性和雄性KO小鼠的穗数都随着成熟而减少。两种基因型的反应持续时间随着年龄的增长而减少，而雄性小鼠的最小阈值降低。最后，我们观察到仅在WT小鼠中，反应潜伏期和强度之间的负相关关系与年龄相关。我们的研究结果表明，雌性KO小鼠和幼龄动物的ICc表现出听觉处理缺陷，这突出了在未来的研究中包括雌性受试者的重要性，以及研究早期发育的重要性，这可能是干预的理想阶段。

{"title":"Alterations in auditory midbrain processing is observed in both female and male mouse model of Fragile X Syndrome","authors":"Abdullah Abdullah , Xiuping Liu , Kartikeya Murari , Jun Yan , Ning Cheng","doi":"10.1016/j.neuroscience.2025.12.062","DOIUrl":"10.1016/j.neuroscience.2025.12.062","url":null,"abstract":"<div><div>Auditory hypersensitivity is a common phenotype in Fragile X Syndrome. Electrophysiology studies at the inferior colliculus of male <em>FMR1-</em>knockout (KO) mice previously demonstrated increased neuronal firing, suggesting that the inferior colliculus is involved in auditory hypersensitivity. Here, we further explored whether the central nucleus of the inferior colliculus (ICc) is involved in auditory hypersensitivity in both female and male KO mice. Tone-evoked <em>in-vivo</em> electrophysiology recordings from ICc neurons of anesthetized (ketamine/xylazine) KO mice at both postnatal day 20 (P20) and 30 (P30) demonstrated increased spikes compared to age- and sex-matched wild-type (WT) mice. Within the KO group, increased spikes were observed in females compared with male mice. Both female and male KO mice also displayed decreased minimum threshold and enhanced response duration at both ages. Additionally, female P30 KO mice displayed weaker inverse relationship between response latency and spike number compared to their WT counterparts. Regarding developmental changes, spike number decreased with maturation in both female and male KO mice. Response duration reduced with age in both sexes of both genotypes, while minimum threshold decreased in the male mice. Finally, we observed an age-related strengthening of the inverse relationship between response latency and magnitude only in the WT mice. Our findings indicate that the ICc display auditory processing deficits particularly in the female KO mice and in young animals highlighting the importance of including female subjects in future studies, and studying early development, which could be an ideal stage for interventions.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 81-92"},"PeriodicalIF":2.8,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Misfolding protein pathology detected in a chronic mouse model of multiple sclerosis 多发性硬化症慢性小鼠模型中错误折叠蛋白的病理检测。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-25 DOI: 10.1016/j.neuroscience.2025.12.063

Tatiana P. MacKeigan , Megan L. Morgan , Sierra Mitchell, Peter K. Stys

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults. The pathobiology of MS includes both autoimmune inflammation and underlying degeneration, with the current challenge being to better understand and treat MS progression. The cuprizone (CPZ) mouse model is commonly used to study de- and remyelination. Despite initial robust myelin repair after toxin withdrawal, mice display progressive callosal atrophy, myelin loss, and gliosis. We tested the hypothesis that this delayed demyelination is due to a progressive degenerative proteopathy. Male C57BL/6 mouse brain sections harvested 8 months after a demyelinating CPZ insult followed by repair were positive for anti-oligomer and anti-fibril epitopes using the antibodies A11 and LOC (p < 0.05 and p < 0.001, respectively). Tissues were also stained with the fluorescent amyloid probes Thioflavin-S (ThS) or pFTAA. Quantitative spectral analysis of the corpus callosum (CC) indicated a subtle but widespread accumulation of ß-sheet-rich material (p < 0.001 and p < 0.0001, respectively). Taken together, our results are consistent with deposition of misfolded proteins facilitating chronic degeneration of axons and myelin in the post-CPZ CC leading to a progressive MS-like pathology. This “late post-CPZ” model could shed light on mechanisms of progressive late degeneration in the MS brain and represents a new animal model of progressive MS, allowing development of novel therapies for this phase of the disease. Our data also raise the possibility that the underlying cytodegenerative component of MS may be driven by subtle toxic amyloid accumulation as in many other traditional neurodegenerative disorders.

多发性硬化症（MS）是年轻人神经功能障碍的最常见原因之一。MS的病理生物学包括自身免疫性炎症和潜在的变性，目前的挑战是更好地理解和治疗MS的进展。铜酮（CPZ）小鼠模型通常用于研究脱髓鞘和髓鞘再生。尽管毒素戒断后最初髓磷脂修复强劲，但小鼠表现出进行性胼胝体萎缩，髓磷脂丢失和胶质瘤。我们检验了这种延迟脱髓鞘是由于进行性退行性蛋白质病的假设。雄性C57BL/6小鼠脑切片在脱髓鞘CPZ损伤和修复后8 个月采集，使用抗体A11和LOC抗低聚物和抗纤维表位阳性(p

{"title":"Misfolding protein pathology detected in a chronic mouse model of multiple sclerosis","authors":"Tatiana P. MacKeigan , Megan L. Morgan , Sierra Mitchell, Peter K. Stys","doi":"10.1016/j.neuroscience.2025.12.063","DOIUrl":"10.1016/j.neuroscience.2025.12.063","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults. The pathobiology of MS includes both autoimmune inflammation and underlying degeneration, with the current challenge being to better understand and treat MS progression. The cuprizone (CPZ) mouse model is commonly used to study de- and remyelination. Despite initial robust myelin repair after toxin withdrawal, mice display progressive callosal atrophy, myelin loss, and gliosis. We tested the hypothesis that this delayed demyelination is due to a progressive degenerative proteopathy. Male C57BL/6 mouse brain sections harvested 8 months after a demyelinating CPZ insult followed by repair were positive for anti-oligomer and anti-fibril epitopes using the antibodies A11 and LOC (p < 0.05 and p < 0.001, respectively). Tissues were also stained with the fluorescent amyloid probes Thioflavin-S (ThS) or pFTAA. Quantitative spectral analysis of the corpus callosum (CC) indicated a subtle but widespread accumulation of ß-sheet-rich material (p < 0.001 and p < 0.0001, respectively). Taken together, our results are consistent with deposition of misfolded proteins facilitating chronic degeneration of axons and myelin in the post-CPZ CC leading to a progressive MS-like pathology. This “late post-CPZ” model could shed light on mechanisms of progressive late degeneration in the MS brain and represents a new animal model of progressive MS, allowing development of novel therapies for this phase of the disease. Our data also raise the possibility that the underlying cytodegenerative component of MS may be driven by subtle toxic amyloid accumulation as in many other traditional neurodegenerative disorders.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 28-36"},"PeriodicalIF":2.8,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spinal dorsal horn GABAergic neuron activation underlies electroacupuncture analgesia in inflammatory pain 脊髓背角gaba能神经元激活是电针镇痛炎症性疼痛的基础。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-24 DOI: 10.1016/j.neuroscience.2025.12.060

Hao Zheng, Xiaoyue Sun, Junkang Chen, Liaoyuxian Deng, Yani Li, Xiaoyu Wang, Yangshuai Su, Xianghong Jing, Zhiyun Zhang

While acupuncture is known to alleviate pain by activating local low-threshold afferents and engaging gate control mechanisms in the spinal cord dorsal horn, the specific role of spinal inhibitory neurons in this process remains unclear. The present study aimed to identify whether A-fiber intensity electroacupuncture (EA) enhances spinal inhibitory tone by recruiting gamma-aminobutyric acidergic (GABAergic) neurons to suppress spinal nociceptive transmission in inflammatory pain. We employed single-fiber recordings on sciatic nerve to determine the A-fiber activation threshold for EA intervention. Behavioral tests confirmed that EA at A-fiber intensity significantly alleviated mechanical hyperalgesia, weight-bearing imbalance, and gait abnormalities in mice with complete Freund’s adjuvant (CFA)-induced inflammatory pain. Transgenic mice with Cre recombinase expression driven by the vesicular GABA transporter promoter (VGAT-Cre) combined with in vivo fiber photometry revealed that this analgesia was associated with enhanced activity of dorsal horn GABAergic neurons. Crucially, chemogenetic activation of GABAergic dorsal horn neurons produced robust analgesic effects, whereas their inhibition increased mechanical sensitivity and enhanced neuronal activation in the superficial laminae of dorsal horn. Furthermore, EA at A-fiber intensity significantly attenuated noxious stimulus-induced neuronal c-Fos expression in the superficial dorsal horn. Notably, optogenetic inhibition of GABAergic neurons reversed EA-induced analgesia. Our results demonstrate that EA at A-fiber intensity alleviates inflammatory pain by recruiting GABAergic neurons in the spinal dorsal horn, thereby enhancing inhibitory tone on spinal nociceptive transmission.

虽然已知针灸通过激活局部低阈值传入神经和参与脊髓背角的门控机制来减轻疼痛，但脊髓抑制神经元在这一过程中的具体作用尚不清楚。本研究旨在确定a纤维强度电针（EA）是否通过募集γ -氨基丁酸能（GABAergic）神经元来抑制炎症性疼痛的脊髓伤害性传递，从而增强脊髓抑制性张力。我们采用坐骨神经单纤维记录来确定EA干预的a -纤维激活阈值。行为学实验证实，a -纤维强度的EA显著缓解了完全性弗氏佐剂（CFA）诱导的炎症性疼痛小鼠的机械性痛觉过敏、负重失衡和步态异常。由囊泡GABA转运子启动子（VGAT-Cre）驱动的Cre重组酶转基因小鼠结合体内纤维光度法显示，这种镇痛与背角GABA能神经元活性增强有关。至关重要的是，对gaba能背角神经元的化学发生操作表明，这些神经元的激活产生镇痛作用，而对它们的抑制增加了机械敏感性以及背角浅层的神经元激活。与此一致的是，a纤维强度的EA显著减弱了有害刺激诱导的浅背角神经元c-Fos的表达。我们的研究结果表明，a纤维强度的EA通过募集脊髓背角的gaba能神经元来减轻炎症性疼痛，从而增强脊髓伤害性传递的抑制性张力。

{"title":"Spinal dorsal horn GABAergic neuron activation underlies electroacupuncture analgesia in inflammatory pain","authors":"Hao Zheng, Xiaoyue Sun, Junkang Chen, Liaoyuxian Deng, Yani Li, Xiaoyu Wang, Yangshuai Su, Xianghong Jing, Zhiyun Zhang","doi":"10.1016/j.neuroscience.2025.12.060","DOIUrl":"10.1016/j.neuroscience.2025.12.060","url":null,"abstract":"<div><div>While acupuncture is known to alleviate pain by activating local low-threshold afferents and engaging gate control mechanisms in the spinal cord dorsal horn, the specific role of spinal inhibitory neurons in this process remains unclear. The present study aimed to identify whether A-fiber intensity electroacupuncture (EA) enhances spinal inhibitory tone by recruiting gamma-aminobutyric acidergic (GABAergic) neurons to suppress spinal nociceptive transmission in inflammatory pain. We employed single-fiber recordings on sciatic nerve to determine the A-fiber activation threshold for EA intervention. Behavioral tests confirmed that EA at A-fiber intensity significantly alleviated mechanical hyperalgesia, weight-bearing imbalance, and gait abnormalities in mice with complete Freund’s adjuvant (CFA)-induced inflammatory pain. Transgenic mice with Cre recombinase expression driven by the vesicular GABA transporter promoter (VGAT-Cre) combined with <em>in vivo</em> fiber photometry revealed that this analgesia was associated with enhanced activity of dorsal horn GABAergic neurons. Crucially, chemogenetic activation of GABAergic dorsal horn neurons produced robust analgesic effects, whereas their inhibition increased mechanical sensitivity and enhanced neuronal activation in the superficial laminae of dorsal horn. Furthermore, EA at A-fiber intensity significantly attenuated noxious stimulus-induced neuronal c-Fos expression in the superficial dorsal horn. Notably, optogenetic inhibition of GABAergic neurons reversed EA-induced analgesia. Our results demonstrate that EA at A-fiber intensity alleviates inflammatory pain by recruiting GABAergic neurons in the spinal dorsal horn, thereby enhancing inhibitory tone on spinal nociceptive transmission.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 37-49"},"PeriodicalIF":2.8,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Optimizing plasticity: the impact of time intervals between priming cTBS and subsequent iTBS on motor-evoked potentials 优化可塑性：启动cTBS和后续iTBS时间间隔对运动诱发电位的影响。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-23 DOI: 10.1016/j.neuroscience.2025.12.056

Ayan Geng , Wenxuan Hu , Junfan Shen , Qinglei Wang , Shizhe Zhu , Youxin Sui , Chaojie Kan , Ying Shen , Tong Wang , Chuan Guo

This study investigated how varying time intervals between priming continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) affect motor cortex plasticity in healthy adults. Using a randomized crossover design, 31 participants underwent four cTBS-iTBS protocols with intervals of 0, 5, 10, or 15 min, with motor-evoked potential (MEP) amplitudes measured at baseline and post-intervention. The results revealed significant main effects of both the stimulation condition and time point on normalized MEP amplitudes. Among the four protocols, the cTBS-10 min-iTBS protocol elicited the greatest facilitatory effect, producing significantly greater MEP enhancement than the 0-, 5-, and 15-minute intervals. The normalized MEP amplitudes showed a time-dependent decline, with the highest values observed at 0 min and the lowest at 30 min post-intervention. These findings suggest that the time intervals between cTBS and iTBS may influence the resulting facilitation effects, offering preliminary evidence that may inform future optimization of TBS-based therapeutic applications.

本研究探讨了启动连续θ波爆发刺激（cTBS）和间歇θ波爆发刺激（iTBS）的不同时间间隔对健康成人运动皮层可塑性的影响。采用随机交叉设计，31名参与者接受了四种cTBS-iTBS方案，间隔为0、5、10或15 min，并在基线和干预后测量运动诱发电位（MEP）振幅。结果表明，刺激条件和时间点对MEP归一化振幅均有显著的主要影响。四种方案中，cTBS-10 min-iTBS方案的促进作用最大，MEP增强效果显著高于0、5、15分钟。标准化的MEP振幅随时间下降，干预后0 min达到最高值，30 min达到最低点。这些发现表明cTBS和iTBS之间的时间间隔可能会影响所产生的促进效应，为未来优化基于tbs的治疗应用提供了初步证据。

{"title":"Optimizing plasticity: the impact of time intervals between priming cTBS and subsequent iTBS on motor-evoked potentials","authors":"Ayan Geng , Wenxuan Hu , Junfan Shen , Qinglei Wang , Shizhe Zhu , Youxin Sui , Chaojie Kan , Ying Shen , Tong Wang , Chuan Guo","doi":"10.1016/j.neuroscience.2025.12.056","DOIUrl":"10.1016/j.neuroscience.2025.12.056","url":null,"abstract":"<div><div>This study investigated how varying time intervals between priming continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) affect motor cortex plasticity in healthy adults. Using a randomized crossover design, 31 participants underwent four cTBS-iTBS protocols with intervals of 0, 5, 10, or 15 min, with motor-evoked potential (MEP) amplitudes measured at baseline and post-intervention. The results revealed significant main effects of both the stimulation condition and time point on normalized MEP amplitudes. Among the four protocols, the cTBS-10 min-iTBS protocol elicited the greatest facilitatory effect, producing significantly greater MEP enhancement than the 0-, 5-, and 15-minute intervals. The normalized MEP amplitudes showed a time-dependent decline, with the highest values observed at 0 min and the lowest at 30 min post-intervention. These findings suggest that the time intervals between cTBS and iTBS may influence the resulting facilitation effects, offering preliminary evidence that may inform future optimization of TBS-based therapeutic applications.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"594 ","pages":"Pages 142-150"},"PeriodicalIF":2.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Alterations of functional connectivity between hyperdirect pathway regions and outside regions in Parkinson’s disease patients with freezing of gait 帕金森病患者步态冻结时超直接通路区域与外部区域功能连通性的改变

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-23 DOI: 10.1016/j.neuroscience.2025.12.058

Yuting Li , Shuwen Bo , Jian-Feng Qu , Xiuhang Ruan , Bin Chen , Mengyan Li , Yujian Zou , Changzheng Shi , Xinhua Wei

Emerging neuroimaging evidence has propelled the formulation of the hypothesis that freezing of gait (FOG) in Parkinson’s disease (PD) arises from dysfunction within the locomotor network. However, to date, there has been a lack of functional connectivity analyses targeting the hyperdirect pathway (HDP) to explore this hypothesis. In this study, we investigate impaired communication within the HDP neural circuitry in FOG patients. Fifty-nine PD patients (33 PD-nFOG and 26 PD-FOG) and thirty matched healthy controls underwent resting-state functional magnetic resonance imaging. Both ROI-wise and voxel-wise based resting-state functional connectivity were calculated in this study. No group differences were observed in the ROI-wise functional connectivity among the regions within the HDP. However, significant reduced functional connectivity based on voxel-wise analysis were observed between the HDP and several brain regions, including the default mode network (DMN), sensorimotor cortex, limbic system and cerebellum in PD, which were associated with psychiatric symptoms, emotional decline, and motor dysfunction. Of note, compared to PD-nFOG, PD-FOG showed increased functional connectivity between the HDP and the cerebellum and the middle occipital gyrus, which was associated with motor impairment in the contralateral limbs. These data extend neuroimaging evidence on that compensatory increased functional connectivity in HDP in FOG patients may indicate a failure compensate for clinical manifestations of limb akinesia, and may represent a loss of low-level automatic control of gait regulation by the basal ganglia.

新出现的神经影像学证据推动了帕金森病（PD）中步态冻结（FOG）由运动网络功能障碍引起的假设的形成。然而，迄今为止，还缺乏针对超直接通路（HDP）的功能连接分析来探索这一假设。在这项研究中，我们研究了FOG患者HDP神经回路中的沟通障碍。59名PD患者（33名PD- nfog和26名PD- fog）和30名匹配的健康对照进行静息状态功能磁共振成像。本研究计算了基于roi和基于体素的静息状态功能连接。在HDP内各区域之间的roi功能连通性方面没有观察到组间差异。然而，基于体素分析，观察到HDP与PD患者的几个脑区（包括默认模式网络（DMN）、感觉运动皮层、边缘系统和小脑）之间的功能连通性显著降低，这些脑区与精神症状、情绪下降和运动功能障碍有关。值得注意的是，与PD-nFOG相比，PD-FOG显示HDP与小脑和枕中回之间的功能连通性增加，这与对侧肢体的运动障碍有关。这些数据扩展了神经影像学证据，证明FOG患者HDP代偿性功能连接增加可能表明肢体运动障碍临床表现的代偿失败，并可能代表基底神经节对步态调节的低水平自动控制的丧失。

{"title":"Alterations of functional connectivity between hyperdirect pathway regions and outside regions in Parkinson’s disease patients with freezing of gait","authors":"Yuting Li , Shuwen Bo , Jian-Feng Qu , Xiuhang Ruan , Bin Chen , Mengyan Li , Yujian Zou , Changzheng Shi , Xinhua Wei","doi":"10.1016/j.neuroscience.2025.12.058","DOIUrl":"10.1016/j.neuroscience.2025.12.058","url":null,"abstract":"<div><div>Emerging neuroimaging evidence has propelled the formulation of the hypothesis that freezing of gait (FOG) in Parkinson’s disease (PD) arises from dysfunction within the locomotor network. However, to date, there has been a lack of functional connectivity analyses targeting the hyperdirect pathway (HDP) to explore this hypothesis. In this study, we investigate impaired communication within the HDP neural circuitry in FOG patients. Fifty-nine PD patients (33 PD-nFOG and 26 PD-FOG) and thirty matched healthy controls underwent resting-state functional magnetic resonance imaging. Both ROI-wise and voxel-wise based resting-state functional connectivity were calculated in this study. No group differences were observed in the ROI-wise functional connectivity among the regions within the HDP. However, significant reduced functional connectivity based on voxel-wise analysis were observed between the HDP and several brain regions, including the default mode network (DMN), sensorimotor cortex, limbic system and cerebellum in PD, which were associated with psychiatric symptoms, emotional decline, and motor dysfunction. Of note, compared to PD-nFOG, PD-FOG showed increased functional connectivity between the HDP and the cerebellum and the middle occipital gyrus, which was associated with motor impairment in the contralateral limbs. These data extend neuroimaging evidence on that compensatory increased functional connectivity in HDP in FOG patients may indicate a failure compensate for clinical manifestations of limb akinesia, and may represent a loss of low-level automatic control of gait regulation by the basal ganglia.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"595 ","pages":"Pages 220-228"},"PeriodicalIF":2.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Advances in how the peripheral immune system interacts with the brain in health and disease 外周免疫系统在健康和疾病中如何与大脑相互作用的研究进展。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-23 DOI: 10.1016/j.neuroscience.2025.12.059

Victor Manuel Ruiz-Rodríguez, Ares Orlando Cuellar-Santoyo, Ana María Estrada-Sánchez

The human body consists of various organs composed of many cells that form complex systems. The brain and immune system are especially interesting because they were once thought to operate independently, with little communication between them. However, the exact pathways connecting the brain and peripheral immune system, as well as their roles in maintaining brain balance or triggering neuropathologies, remain unclear. This review outlines the components of the immune system within the brain. Next, we elaborate on new evidence demonstrating that, in the brain, mast cells serve as neuroimmune sentinels, and that perivascular spaces, the skull’s bone marrow, and meningeal lymphatic innervation coordinate brain immunity. This evidence uncovers a close interaction between the brain and the peripheral immune system. Additionally, recent findings on neurotransmitter-immune crosstalk and the role of miRNA-loaded exosomes in long-range peripheral signaling may outline potential regulatory pathways between the peripheral immune system and the brain. Finally, we highlight that changes in the mechanisms of interaction between the brain and the immune system are linked to the development and progression of various diseases. A deeper understanding of the connection between the immune and nervous systems could yield new insights into the causes of neuropathologies, neurodegenerative diseases, and immune-related disorders, potentially opening new avenues for treatment.

人体由各种器官组成，这些器官由许多细胞组成复杂的系统。大脑和免疫系统特别有趣，因为它们曾经被认为是独立运作的，彼此之间几乎没有交流。然而，连接大脑和外周免疫系统的确切途径，以及它们在维持大脑平衡或触发神经病变中的作用，仍不清楚。这篇综述概述了大脑免疫系统的组成部分。接下来，我们详细阐述了新的证据表明，在大脑中，肥大细胞充当神经免疫哨兵，血管周围空间，颅骨骨髓和脑膜淋巴神经支配协调大脑免疫。这一证据揭示了大脑和外周免疫系统之间的密切相互作用。此外，最近关于神经递质-免疫串扰和mirna负载外泌体在远距离外周信号传导中的作用的发现可能概述外周免疫系统和大脑之间的潜在调节途径。最后，我们强调大脑和免疫系统之间相互作用机制的变化与各种疾病的发生和进展有关。对免疫系统和神经系统之间联系的更深入了解可能会对神经病理学、神经退行性疾病和免疫相关疾病的病因产生新的见解，可能会为治疗开辟新的途径。

{"title":"Advances in how the peripheral immune system interacts with the brain in health and disease","authors":"Victor Manuel Ruiz-Rodríguez, Ares Orlando Cuellar-Santoyo, Ana María Estrada-Sánchez","doi":"10.1016/j.neuroscience.2025.12.059","DOIUrl":"10.1016/j.neuroscience.2025.12.059","url":null,"abstract":"<div><div>The human body consists of various organs composed of many cells that form complex systems. The brain and immune system are especially interesting because they were once thought to operate independently, with little communication between them. However, the exact pathways connecting the brain and peripheral immune system, as well as their roles in maintaining brain balance or triggering neuropathologies, remain unclear. This review outlines the components of the immune system within the brain. Next, we elaborate on new evidence demonstrating that, in the brain, mast cells serve as neuroimmune sentinels, and that perivascular spaces, the skull’s bone marrow, and meningeal lymphatic innervation coordinate brain immunity. This evidence uncovers a close interaction between the brain and the peripheral immune system. Additionally, recent findings on neurotransmitter-immune crosstalk and the role of miRNA-loaded exosomes in long-range peripheral signaling may outline potential regulatory pathways between the peripheral immune system and the brain. Finally, we highlight that changes in the mechanisms of interaction between the brain and the immune system are linked to the development and progression of various diseases. A deeper understanding of the connection between the immune and nervous systems could yield new insights into the causes of neuropathologies, neurodegenerative diseases, and immune-related disorders, potentially opening new avenues for treatment.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"596 ","pages":"Pages 24-35"},"PeriodicalIF":2.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Acute administration of a dual orexin receptor antagonist attenuates sleep fragmentation in a mouse model of traumatic brain injury 急性给予双食欲素受体拮抗剂可减轻创伤性脑损伤小鼠模型的睡眠碎片。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-23 DOI: 10.1016/j.neuroscience.2025.12.057

Sean D. Carey , Allison J. Gibbons , John A. Craig , Hryhoriy Zhoba , Jessica A. Babb , Gary B. Kaplan , Mark R. Zielinski

Traumatic brain injuries (TBI) induce persistent sleep dysregulation. We aimed to determine if a dual orexin receptor antagonist (DORA) could improve sleep dysregulation acutely in mice after TBI across multiple timepoints after an injury to mimic as needed clinical interventions. Male and female C57BL/6J mice (N = 5–8 per treatment group) received a TBI by controlled cortical impact or sham surgery (SHAM). Sleep architecture was assessed at baseline and after vehicle (VEH) or DORA (Lemborexant) given by gavage 24 hours (H), 2 weeks (W), 1 month (M), or 2 M post-TBI. TBI produced increases in non-rapid eye movement sleep (NREMS) amounts and waking EEG delta, theta, and alpha power 24 H post-injury compared to baseline measures and reductions in these measures 1–2 months post-injury. TBI-DORA condition had no effect on acute TBI sleep amount and EEG power effects. However, increased waking frequencies were observed at 1 M in the TBI-VEH group during the light period and were not significantly different from baseline at 1 M in the TBI-DORA group, suggesting an effect on sleep fragmentation. A return to baseline NREMS was also observed in TBI-DORA groups at 1 M looking at average NREMS duration across Zeitgeber Time (ZT) during the light period. DORA treatment reduced sleep latency during the multiple sleep latency test (MSLT) in all groups. Overall, these data suggest that acute interventional DORA treatment can inhibit persistent sleep fragmentation and reverse increased wakefulness after TBI.

外伤性脑损伤（TBI）可诱发持续性睡眠失调。我们的目的是确定双重食欲素受体拮抗剂（DORA）是否可以在创伤后多个时间点急性改善脑外伤小鼠的睡眠失调，以模拟需要的临床干预。雄性和雌性C57BL/6J小鼠（N = 每个治疗组5-6只）通过控制皮质撞击或假手术（sham）接受TBI。在颅脑损伤后基线和载药后（VEH）或灌胃给予DORA (Lemborexant) 24 h (h)、2 周(W)、1 个月(M)或2 M时评估睡眠结构。与基线测量值相比，创伤后24小时，TBI产生的非快速眼动睡眠（NREMS）量和清醒脑电图δ、θ和α功率增加，而这些测量值在损伤后1-2个月 后减少。TBI- dora状态对急性TBI睡眠量和脑电功率无影响。然而，在1 M时，TBI-VEH组在光照期观察到清醒频率增加，而在1 M时，TBI-DORA组与基线没有显著差异，这表明对睡眠碎片化有影响。TBI-DORA组在1 M时也观察到NREMS恢复到基线水平，并观察光照期间整个授时时间（ZT）的平均NREMS持续时间。在多次睡眠潜伏期试验（MSLT）中，DORA治疗降低了所有组的睡眠潜伏期。总的来说，这些数据表明急性介入DORA治疗可以抑制TBI后持续的睡眠碎片化和逆转觉醒增加。

{"title":"Acute administration of a dual orexin receptor antagonist attenuates sleep fragmentation in a mouse model of traumatic brain injury","authors":"Sean D. Carey , Allison J. Gibbons , John A. Craig , Hryhoriy Zhoba , Jessica A. Babb , Gary B. Kaplan , Mark R. Zielinski","doi":"10.1016/j.neuroscience.2025.12.057","DOIUrl":"10.1016/j.neuroscience.2025.12.057","url":null,"abstract":"<div><div>Traumatic brain injuries (TBI) induce persistent sleep dysregulation. We aimed to determine if a dual orexin receptor antagonist (DORA) could improve sleep dysregulation acutely in mice after TBI across multiple timepoints after an injury to mimic as needed clinical interventions. Male and female C57BL/6J mice (N = 5–8 per treatment group) received a TBI by controlled cortical impact or sham surgery (SHAM). Sleep architecture was assessed at baseline and after vehicle (VEH) or DORA (Lemborexant) given by gavage 24 hours (H), 2 weeks (W), 1 month (M), or 2 M post-TBI. TBI produced increases in non-rapid eye movement sleep (NREMS) amounts and waking EEG delta, theta, and alpha power 24 H post-injury compared to baseline measures and reductions in these measures 1–2 months post-injury. TBI-DORA condition had no effect on acute TBI sleep amount and EEG power effects. However, increased waking frequencies were observed at 1 M in the TBI-VEH group during the light period and were not significantly different from baseline at 1 M in the TBI-DORA group, suggesting an effect on sleep fragmentation. A return to baseline NREMS was also observed in TBI-DORA groups at 1 M looking at average NREMS duration across Zeitgeber Time (ZT) during the light period. DORA treatment reduced sleep latency during the multiple sleep latency test (MSLT) in all groups. Overall, these data suggest that acute interventional DORA treatment can inhibit persistent sleep fragmentation and reverse increased wakefulness after TBI.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"594 ","pages":"Pages 190-202"},"PeriodicalIF":2.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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