Brain Research Bulletin最新文献_第2页

The role of optic flow on reactive brain processing in cognitive tasks during locomotion 运动认知任务中光流在反应性脑加工中的作用。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-08 DOI: 10.1016/j.brainresbull.2026.111722

BiancaMaria Di Bello , Natalie Ferrulli , Camilla Panacci , Margherita Filosa , Sabrina Pitzalis , Francesco Di Russo

Perception and action share neural resources that must be flexibly allocated across simultaneous tasks. In this context, the optic flow provides key visual input during locomotion and may interact with concurrent cognitive processing. This study aimed to: 1) examine how walking modulates event-related potential (ERP) components linked to visual, attentional, and sensorimotor processes evoked by a concomitant cognitive task; 2) relate neural changes to behavior; 3) test whether optic flow modifies these locomotion effects; and 4) extend previous findings on anticipatory brain processing to post-stimulus activity. To these aims, forty participants performed a visual discrimination task under four conditions that manipulated locomotion (walking vs. standing) and visual stimulation (with vs. without optic flow). Behavioral measures (response time (RT), accuracy, RT variability) and ERP components indexing distinct brain processing stages were recorded. Behaviorally, walking improved performance by increasing accuracy and reducing RT variability, while optic flow reduced accuracy without affecting RT. At the brain level, walking decreased the prefrontal N1 (pN1), indicating lower visual awareness, but increased the N1 (enhanced visual attention). Walking with the optic flow also increased the prefrontal P1 (pP1), indicating greater sensorimotor awareness. The presence of the optic flow independently reduced P1 (associated with early visual processing) and increased the pN1 and the N1. The P3 varied only with stimulus type, indicating no walking or optic flow effects on post-perceptual evaluation. Overall, walking facilitated early cognitive processing, whereas the optic flow added sensory-attentional load, reducing accuracy via competition for visual resources. These results support multiple-resource allocation dual-task theories, highlighting how ecological multisensory environments may dynamically reallocate cognitive resources and shape neural processing during action. In addition, present data can be used to design immersive environments, motor-cognitive dual-task training, and real-world cognition studies.

感知和行动共享神经资源，这些资源必须在同时进行的任务中灵活分配。在这种情况下，光流在运动过程中提供关键的视觉输入，并可能与并发的认知加工相互作用。本研究旨在：1)研究步行如何调节伴随认知任务诱发的与视觉、注意和感觉运动过程相关的事件相关电位（ERP）成分；2)将神经变化与行为联系起来；3)测试光流是否改变了这些运动效果；4)将先前关于预期脑加工的发现扩展到刺激后活动。为了达到这些目的，40名参与者在操纵运动（行走与站立）和视觉刺激（有光流与无光流）的四种条件下完成了视觉辨别任务。记录行为测量（反应时间、准确性、反应时间变异性）和标记不同脑加工阶段的ERP成分。在行为上，步行通过提高准确性和降低RT变异性来改善表现，而光流降低准确性，但不影响RT。在大脑水平上，步行降低前额叶N1 (pN1)，表明视觉意识降低，但增加N1（增强视觉注意）。伴随光流行走也增加了前额叶P1 (pP1)，表明更强的感觉运动意识。光流的存在独立地降低了P1（与早期视觉处理有关）并增加了pN1和N1。P3仅随刺激类型而变化，表明行走或光流对知觉后评价没有影响。总的来说，走路促进了早期的认知加工，而光流增加了感觉-注意力负荷，通过竞争视觉资源降低了准确性。这些结果支持了多资源分配双任务理论，强调了生态多感官环境如何动态重新分配认知资源并在行动过程中塑造神经处理。此外，现有数据可用于设计沉浸式环境、运动-认知双任务训练和现实世界认知研究。

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引用次数: 0

The impact of sleep deprivation on dynamic functional connectivity of the brain: Based on alertness task performance 睡眠剥夺对大脑动态功能连接的影响：基于警觉性任务表现

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-08 DOI: 10.1016/j.brainresbull.2025.111712

Anping Ouyang , Xinxin Lin , Tian Zhang , Jiayao Li , Chenxi Li , Lingling Wang , Zhiyuan Cao , Xuqian Diao , Wei He , Qianqian Dong , Jun Jiang , Peng Fang

Sleep deprivation (SD) impairs mood and cognition, yet its dynamic neural mechanisms remain unclear. Forty healthy adults (30-h SD) completed mood assessments, resting-state fMRI (rs-fMRI), and psychomotor vigilance task (PVT) tests at baseline and post-SD. Using dynamic functional connectivity (dFC) with sliding windows and k-means clustering, we identified two recurrent whole-brain states: (i) an economical state with sparse, weaker global coupling and (ii) a maladaptive compensatory state with globally strengthened synchronization. SD increased both the fraction of windows and mean dwell time (MDT) of the maladaptive state. Across participants, PVT lapses correlated positively with the maladaptive state’s MDT and fraction of windows and negatively with those of the economical state. Finally, we built an interpretable predictive model of PVT lapses using competitive adaptive reweighted sampling partial least-squares regression (CARS-PLSR), which highlighted connections within the dorsal attention network (DAN) as key predictors. These findings link behavioral impairment to altered brain-state dynamics and provide a sparse, testable feature set that can support early risk stratification and intervention for SD-related cognitive decline.

睡眠剥夺损害情绪和认知，但其动态神经机制尚不清楚。40名健康成人（30小时SD）在基线和SD后完成情绪评估、静态功能磁共振成像（rs-fMRI）和精神运动警觉性任务（PVT）测试。利用滑动窗口和k-means聚类的动态功能连接（dFC），我们确定了两种循环的全脑状态：(i)具有稀疏的、较弱的全局耦合的经济状态和（ii）具有全局增强同步的不适应补偿状态。SD增加了非适应状态的窗口数和平均停留时间（MDT）。在所有被试中，PVT失误与适应不良状态的MDT和窗的比例正相关，与经济状态的MDT和窗的比例负相关。最后，我们使用竞争自适应重加权抽样偏最小二乘回归（CARS-PLSR）建立了一个可解释的PVT失误预测模型，该模型突出了背侧注意网络（DAN）内的连接作为关键预测因子。这些发现将行为障碍与改变的大脑状态动力学联系起来，并提供了一个稀疏的、可测试的特征集，可以支持sd相关认知衰退的早期风险分层和干预。

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引用次数: 0

Decoding neurotransmitter and genetic contributions to abnormal neuronal signal variability in Anti‑N‑Methyl‑D‑Aspartate receptor encephalitis: Implications for targeted therapies 解码神经递质和基因对抗N甲基D天冬氨酸受体脑炎异常神经元信号变异性的贡献：对靶向治疗的影响

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-01 DOI: 10.1016/j.brainresbull.2026.111717

Rong Guo , Wenjia Wang , Rui Qian , Yang Ji , Wei Li , Meidan Zu , Qianqian Li , Jiayun Wu , Wentao Dai , Si Xu , Juanjuan Zhang , Ling Wei , Yuanyuan Guo , Yanghua Tian , Kai Wang

Background

The molecular mechanisms linking brain function alterations to gene expression in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis remain unclear.

Methods

We analyzed the coefficient of variation of blood oxygenation level dependent signal (CV_BOLD) and functional connectivity (FC) in 30 healthy controls and 42 patients, with classification via 5 machine learning models. Transcriptomic profiles from the Allen Human Brain Atlas and neurotransmitter density maps from positron emission tomography were integrated. Partial least squares (PLS) regression determined gene expression relevant to the CV_BOLD/FC changes. Multivariate linear regression evaluated neurotransmitter contributions.

Results

Anti-NMDAR encephalitis patients exhibited increased CV_BOLD in the right superior parietal gyrus, right fusiform gyrus, right lingual gyrus, left fusiform gyrus and left paracentral lobule meanwhile disrupted FC mainly in default mode and salience networks. PLS analysis revealed 2320 genes significantly associated with CV_BOLD/FC (p_bonferrni < 0.05), enriched in synaptic signaling (MAPK, cAMP), metabolic regulation (insulin resistance), and neurodegeneration pathways. Hub genes PPARGC1A (positive correlation with CV_BOLD/FC) and UBA52 (negative correlation) were validated in key brain regions. Neurotransmitter analysis showed norepinephrine (NAT) strongly contributed to CV_BOLD (weight = 0.57, p_FDR < 0.001), meanwhile serotonin (5HT4), cannabinoid (CB1), noradrenaline (NAT), and glutamate (NMDA) influenced FC.

Conclusion

This study identifies a transcriptional signature that is spatially associated with CV_BOLD/FC abnormalities and neurotransmitter distributions in anti-NMDAR encephalitis, thereby generating hypotheses about molecular targets that may be relevant for future mechanistic studies and precision medicine.

抗n -甲基- d -天冬氨酸受体（NMDAR）脑炎脑功能改变与基因表达之间的分子机制尚不清楚。方法分析30例健康对照和42例患者的血氧水平依赖信号（CVBOLD）变异系数和功能连通性（FC），并通过5种机器学习模型进行分类。来自艾伦人脑图谱的转录组谱和来自正电子发射断层扫描的神经递质密度图被整合。偏最小二乘（PLS）回归确定了与CVBOLD/FC变化相关的基因表达。多元线性回归评估神经递质的贡献。结果抗nmdar脑炎患者右侧顶叶上回、右侧梭状回、右侧舌回、左侧梭状回和左侧中央旁小叶的CVBOLD增加，同时主要在默认模式和突出网络中破坏FC。PLS分析显示2320个基因与CVBOLD/FC显著相关（phbonferrni < 0.05），这些基因丰富于突触信号传导（MAPK、cAMP）、代谢调节（胰岛素抵抗）和神经退行性途径。中枢基因PPARGC1A（与CVBOLD/FC正相关）和UBA52（负相关）在关键脑区得到验证。神经递质分析显示，去甲肾上腺素（NAT）对CVBOLD有显著影响（weight = 0.57, pFDR < 0.001），同时血清素（5HT4）、大麻素（CB1）、去甲肾上腺素（NAT）和谷氨酸（NMDA）影响FC。结论本研究确定了抗nmdar脑炎中与CVBOLD/FC异常和神经递质分布存在空间关联的转录特征，从而提出了可能与未来机制研究和精准医学相关的分子靶点假设。

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引用次数: 0

A vagus-dependent gut microbiota–metabolite axis drives chronic inflammatory pain and working-memory deficits in mice 迷走神经依赖的肠道微生物代谢物轴驱动小鼠慢性炎症性疼痛和工作记忆缺陷。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-01 DOI: 10.1016/j.brainresbull.2025.111702

Cai-bao Yue , Wei-wei Luan , Di Qiu , Xin Ding , Han-Wen Gu , Pan-Miao Liu , Kenji Hashimoto , Jian-Jun Yang , Xing-Ming Wang

Chronic inflammatory pain (CIP) has been increasingly linked to gut microbiota (GM)–brain interactions, yet whether these effects rely on vagal signaling remains unclear. Here, we investigated whether GM from CIP mice is sufficient to transfer pain-like behaviors to healthy recipients and whether this process depends on the vagus nerve. Fecal microbiota transplantation (FMT) from mice treated with complete Freund’s adjuvant induced mechanical and thermal hypersensitivity and impaired working memory in recipients, accompanied by hippocampal neuroinflammation and GM dysbiosis. Subdiaphragmatic vagotomy (SDV) performed prior to FMT attenuated these behavioral and neuroinflammatory alterations and partially normalized microbial community structure. Plasma metabolomics further showed that SDV restored phosphatidylcholines while reducing pro-inflammatory lipid classes, with several metabolites and bacterial taxa correlating significantly with pain sensitivity and hippocampal cytokine levels. Collectively, these findings demonstrate that a vagus-dependent GM–metabolite–brain axis contributes to CIP-like behaviors and neuroinflammation. Targeting vagal pathways and GM-regulated lipid metabolism may offer therapeutic strategies and pharmacodynamic biomarkers for inflammatory pain.

慢性炎症性疼痛（CIP）越来越多地与肠道微生物群(GM)-大脑相互作用联系在一起，但这些作用是否依赖于迷走神经信号尚不清楚。在这里，我们研究了CIP小鼠的GM是否足以将疼痛样行为转移到健康受体，以及这一过程是否依赖于迷走神经。接受完全弗氏佐剂治疗的小鼠粪便微生物群移植（FMT）诱导受者机械和热超敏反应和工作记忆受损，并伴有海马神经炎症和GM生态失调。在FMT之前进行的膈下迷走神经切开术（SDV）减轻了这些行为和神经炎症的改变，并部分正常化了微生物群落结构。血浆代谢组学进一步表明，SDV恢复磷脂酰胆碱，同时降低促炎脂类，几种代谢物和细菌分类与疼痛敏感性和海马细胞因子水平显著相关。总的来说，这些发现表明迷走神经依赖的gm -代谢物-脑轴有助于cip样行为和神经炎症。靶向迷走神经通路和转基因调节的脂质代谢可能为炎症性疼痛提供治疗策略和药效学生物标志物。

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引用次数: 0

The uptake of β-amyloid by various brain cells exhibits heterogeneity and correlates with the CD14 expression 不同脑细胞对β-淀粉样蛋白的摄取表现出异质性，并与CD14表达相关。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-01 DOI: 10.1016/j.brainresbull.2025.111699

Jingming Shi , Yandong Ma , Lei Gao , Yuting Dai , Qian Chen , Xudong Li , Hang Liu , Ruotong Li , Jie Zhang , Chaoren Yan

The involvement of β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD) remains a contentious topic within the scientific community. For a long time, many studies have been highly interested in the topic of brain cells internalizing Aβ. Nonetheless, the precise processes and mechanisms underlying Aβ internalization by neurons, astrocytes, and microglia under AD settings have yet to be clarified. This study investigated primary neurons and glial cells cultured in vitro, as well as APP/PS1 mouse models. Laser confocal microscopy, frozen brain sections, and intraventricular injection in mice and other methods were employed to evaluate the uptake of Aβ42 monomers and oligomers (ADDL) by neurons, microglia, astrocytes. The results revealed that both microglia and neurons internalized Aβ oligomers. In the experiment, the Aβ that adhered to the cells, as visible using the laser confocal microscope, likely comprised two components: the portion that attached to the cells and the portion that was internalized by them. Contrary to prior observations, astrocytes exhibited limited in ability to internalize Aβ oligomers. The disparities in internalization across the three cell types were probably associated with CD14. This work elucidated the intricacies of several different types of cells internalization of Aβ processes and support a crucial role for CD14 in regulating Aβ internalization.

β-淀粉样蛋白（a β）在阿尔茨海默病（AD）发病中的作用在科学界仍然是一个有争议的话题。长期以来，许多研究都对脑细胞内化a β的问题非常感兴趣。尽管如此，AD环境下神经元、星形胶质细胞和小胶质细胞内化Aβ的确切过程和机制尚不清楚。本研究研究了体外培养的原代神经元和胶质细胞，以及APP/PS1小鼠模型。采用激光共聚焦显微镜、冷冻脑切片、小鼠脑室内注射等方法评价神经元、小胶质细胞、星形胶质细胞对Aβ42单体和寡聚物（ADDL）的摄取。结果表明，小胶质细胞和神经元都内化了Aβ低聚物。在实验中，使用激光共聚焦显微镜可以看到粘附在细胞上的Aβ可能由两部分组成：附着在细胞上的部分和被细胞内化的部分。与先前的观察相反，星形胶质细胞内化Aβ低聚物的能力有限。三种细胞类型的内化差异可能与CD14有关。这项工作阐明了几种不同类型的细胞内化a β过程的复杂性，并支持CD14在调节a β内化中的关键作用。

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引用次数: 0

How tobacco use disorder affects gray matter aberrance: The mediating effect of glymphatic system function 烟草使用障碍如何影响灰质异常：淋巴系统功能的中介作用

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-01 DOI: 10.1016/j.brainresbull.2026.111725

Mengzhe Zhang , Bohui Mei , Longyao Ma , Kaixin Li , Mengzhu Wang , Weijian Wang , Yong Zhang

Background

The glymphatic system (GS) represents a newly identified biological pathway, but its possible involvement in the pathophysiology of tobacco use disorder (TUD) remains unclear. We aimed to assess the GS function in TUD individuals and to establish the connections among GS, brain structure and clinical features of disease.

Methods

We recruited 149 male subjects, including 92 TUD individuals and 57 controls, then obtained their 3D-T1 weighted image scans, diffusion tensor image scans and clinical scales. Diffusion tensor imaging along the perivascular space (DTI-ALPS) index was calculated to evaluate glymphatic function changes between the groups. Gray matter (GM) regions associated with the DTI-ALPS index were identified by voxel-based morphometry analysis (VBM). Finally, the relationships between DTI-ALPS index, GM and smoking behaviors were assessed through a mediation model.

Results

Compared to control group, TUD group displayed notably lower DTI-ALPS index in the whole brain and both bilateral hemispheres, which displayed negatively correlations with the severity of disease. The GMV alterations in left thalamus and right inferior temporal gyrus were positively correlated with the mean DTI-ALPS index. Moreover, the DTI-ALPS index partially mediated the relationship between GMV alterations and pack-year in TUD.

Conclusions

The current study revealed abnormalities of DTI-ALPS index in TUD and identified that abnormal GS function in TUD individuals could be the potential mechanism underlying the effects of tobacco exposure on GMV changes. These findings provided further evidence for understanding the pathogenesis of TUD and suggested GS function could serve as a new target for clinical therapeutic strategies.

glymphatic system （GS）是一种新发现的生物学途径，但其在烟草使用障碍（TUD）病理生理中的可能参与尚不清楚。我们的目的是评估TUD个体的GS功能，并建立GS与大脑结构和疾病临床特征之间的联系。方法招募男性受试者149例，其中TUD组92例，对照组57例，获取其3D-T1加权图像扫描、弥散张量图像扫描和临床量表。计算沿血管周围间隙弥散张量成像（DTI-ALPS）指数，评价各组间淋巴功能的变化。通过基于体素的形态分析（VBM），确定与DTI-ALPS指数相关的灰质（GM）区域。最后，通过中介模型评估DTI-ALPS指数、GM与吸烟行为之间的关系。结果与对照组相比，TUD组全脑及双侧半脑DTI-ALPS指数明显降低，且与疾病严重程度呈负相关。左侧丘脑和右侧颞下回GMV变化与DTI-ALPS平均指数呈正相关。此外，DTI-ALPS指数部分介导了TUD GMV变化与包年之间的关系。结论本研究揭示了TUD患者DTI-ALPS指数异常，认为TUD患者GS功能异常可能是烟草暴露影响GMV变化的潜在机制。这些发现为了解TUD的发病机制提供了进一步的证据，并提示GS功能可作为临床治疗策略的新靶点。

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引用次数: 0

VPS25 alleviates depression-like behavior in rats by inhibiting apoptosis in the hippocampus VPS25通过抑制海马细胞凋亡减轻大鼠抑郁样行为。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-01 DOI: 10.1016/j.brainresbull.2025.111705

Lili Yuan , Xiaofang Huang , Qi Wang , Beibei Hou , Sifan Xu , Zhiming Zhou , Yigao Wu , Jiucui Tong

Background

Depression is a psychiatric disorder manifested by significant and persistent depressive symptoms. In recent years, autophagy has been identified with a key role in neuronal survival, synaptic plasticity, and depression. We previously observed that vacuolar protein sorting 25 (VPS25) was up-regulated in the hippocampus of depressive rats, but the mechanisms were unclear.

Methods

In chronic unpredictable mild stress (CUMS)-stimulated rats, lateral ventricles were injected with adeno-associated virus (AAV) to silence VPS25. Depression status in rats was evaluated using behavioral tests. In the corticosterone (CORT)-induced PC12 cell apoptosis model, Cell Counting Kit-8 (CCK-8) assays were used to determine cell viability. We next investigated the effects of CORT and VPS25 on PC12 apoptosis and proliferation using flow cytometry and cell proliferation assays. VPS25 mRNA expression was determined using qRT-PCR, while VPS25, Bax, Bcl-2, cleaved-caspase3, P62, Beclin-1, LC3, JAK1, p-JAK1, STAT1, and p-STAT1 levels of expression were assessed using western blotting.

Results

Our data demonstrate that in CORT-induced PC12 cells or a CUMS-induced rat depression model, VPS25 silencing not only alleviated CUMS-induced neuronal apoptosis in rats but also reduced CORT-induced apoptosis in PC12 cells. Notably, VPS25 silencing alleviated CUMS-provoked depression-like behaviors, reduced neuronal apoptosis (as evidenced by TUNEL staining), and promoted autophagy flux by increasing the LC3-II/LC3-I ratio. These effects were associated with the blockade of JAK/STAT signaling.

Conclusion

These results indicate that silencing VPS25 alleviates depression symptoms by promoting autophagy and inhibiting neuronal apoptosis, partly through the JAK/STAT signaling pathway.

背景：抑郁症是一种精神障碍，表现为显著和持续的抑郁症状。近年来，自噬在神经元存活、突触可塑性和抑制中起着关键作用。我们之前观察到抑郁大鼠海马中空泡蛋白分选25 （VPS25）上调，但机制尚不清楚。方法：在慢性不可预测轻度应激（CUMS）刺激的大鼠侧脑室注射腺相关病毒（AAV）以沉默VPS25。用行为测试评估大鼠的抑郁状态。在皮质酮（CORT）诱导的PC12细胞凋亡模型中，采用细胞计数试剂盒-8 （CCK-8）检测细胞活力。接下来，我们利用流式细胞术和细胞增殖实验研究了CORT和VPS25对PC12细胞凋亡和增殖的影响。采用qRT-PCR检测VPS25 mRNA的表达，western blotting检测VPS25、Bax、Bcl-2、cleaved-caspase3、P62、Beclin-1、LC3、JAK1、p-JAK1、STAT1和p-STAT1的表达水平。结果：我们的数据表明，在cort诱导的PC12细胞或cms诱导的大鼠抑郁模型中，VPS25沉默不仅减轻了cms诱导的大鼠神经元凋亡，而且减少了cort诱导的PC12细胞凋亡。值得注意的是，VPS25沉默可减轻cms引起的抑郁样行为，减少神经元凋亡（TUNEL染色证实），并通过增加LC3-II/LC3-I比值促进自噬通量。这些效应与阻断JAK/STAT信号通路有关。结论：这些结果表明，沉默VPS25可通过促进自噬和抑制神经元凋亡来缓解抑郁症状，部分途径是通过JAK/STAT信号通路。

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引用次数: 0

Cerebellar deep brain stimulation rescues Purkinje cell mitochondrial density in a genetic mouse model of cerebellar ataxia 小脑深部脑刺激可恢复遗传性小脑共济失调小鼠模型中的浦肯野细胞线粒体密度。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-01 DOI: 10.1016/j.brainresbull.2025.111704

Lauren N. Miterko-Myers , Lauren E. Peacoe , Lita Duraine , Zhongyuan Zuo , Roy V. Sillitoe

Deep brain stimulation (DBS) improves motor function in a growing list of movement diseases including Parkinson’s disease, dystonia, and tremor. There is evidence that DBS may also be effective in ataxia. It is not known why DBS is effective, but modulating cell activity and conferring neuroprotection are hypothesized to underlie its benefits. Understanding the effects of DBS on neurons is paramount to extending its clinical use in the treatment of various motor and non-motor diseases. Here, we stimulated the cerebellum of Car8 waddles (Car8^wdl) mice, given the cerebellum’s important role in ataxia pathophysiology. Using transmission electron microscopy, we tested the effects of therapeutic neuromodulation on Purkinje cell subcellular structures, including the mitochondria and their proximity to the endoplasmic reticulum (ER). In the absence of stimulation, we found increased putative mitochondria-ER contacts in Car8^wdl Purkinje cells as well as mitochondrial size and density alterations. Low-frequency cerebellar DBS rescued mitochondrial density, but not size or putative contacts in Car8^wdl Purkinje cells. Although increased mitochondrial density and sustained ER contact are specific to DBS treatment, they do not determine efficaciousness. These data uncover a mode of intracellular plasticity in Purkinje cells after stimulation, enhancing our mechanistic understanding of DBS for cerebellar disorders.

脑深部电刺激（DBS）可以改善越来越多的运动疾病的运动功能，包括帕金森病、肌张力障碍和震颤。有证据表明，DBS可能对共济失调也有效。目前尚不清楚DBS为什么有效，但假设调节细胞活动和赋予神经保护是其益处的基础。了解DBS对神经元的影响对于扩大其在各种运动和非运动疾病治疗中的临床应用至关重要。考虑到小脑在共济失调病理生理中的重要作用，我们对Car8 waddle小鼠的小脑进行了刺激。利用透射电镜，我们测试了治疗性神经调节对浦肯野细胞亚细胞结构的影响，包括线粒体及其与内质网（ER）的接近性。在没有刺激的情况下，我们发现Purkinje细胞中线粒体-内质网接触增加，线粒体大小和密度也发生了变化。低频小脑DBS可以挽救Car8wdl浦肯野细胞的线粒体密度，但不能挽救细胞大小或推测的接触。虽然增加的线粒体密度和持续的内质网接触是DBS治疗所特有的，但它们并不能决定疗效。这些数据揭示了浦肯野细胞在刺激后的细胞内可塑性模式，增强了我们对DBS治疗小脑疾病的机制理解。

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引用次数: 0

Investigation of dipyridamole-elicited signaling in the brain of Niemann Pick type C mice: A multi-omic study 双嘧达莫诱导的niemann pick c型小鼠脑内信号传导的多组学研究。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-01 DOI: 10.1016/j.brainresbull.2025.111708

Sabrina Tait , Federica Fratini , Zaira Boussadia , Lucia Gaddini , Manuela Marra , Loredana Le Pera , Gloria Venturini , Antonella Ferrante

Niemann Pick type C1 (NPC1) is a rare, fatal disorder characterized by endo-lysosomal (EL) lipid accumulation that leads to damage of both peripheral organs and central nervous system, with cerebellum and hippocampus being particularly affected. Currently very few therapeutic options exist in Europe for NPC. In fact, miglustat is the only approved drug and L-acetylleucine was recently granted for marketing authorization by European Medicine Agency. Thus, the identification of new treatments is mandatory. We have previously demonstrated that dipyridamole (DIP), an approved medicine that is clinically employed as an antiplatelet agent, could rescue recognition memory and increase hippocampal expression of calbindin. On the contrary, the drug was unable to improve cerebellar-dependent motor function. In order to elucidate the mechanism of these region-specific changes induced by DIP, in this work we performed a multi-omic analysis of genes and proteins modulated by the treatment in the hippocampus and cerebellum of a mouse model of NPC1 (Npc1^-/-). Our results revealed that DIP significantly affected various pathways in the hippocampus at protein level, but it had no significant impact on pathways in the cerebellum (either at gene or protein level). Interestingly, the most affected pathways in the hippocampus of Npc1^-/- mice administered with DIP were those related to cGMP-PKG activation and to mitochondrial function. Our results paved the way to test DIP in experimental models of other neurodegenerative disorders, such as Alzheimer’s disease that is similarly marked by hippocampal and mitochondrial dysfunctions.

Niemann Pick type C1 （NPC1）是一种罕见的致死性疾病，其特征是内溶酶体（EL）脂质积聚，可导致外周器官和中枢神经系统损害，小脑和海马尤其受影响。目前在欧洲针对鼻咽癌的治疗方案很少。事实上，米卢司他是唯一被批准的药物，l -乙酰亮氨酸最近被欧洲药品管理局批准上市。因此，确定新的治疗方法是必须的。我们之前已经证明，临床上被批准用作抗血小板药物的双嘧达莫（DIP）可以恢复识别记忆并增加海马calbindin的表达。相反，该药物不能改善小脑依赖性运动功能。为了阐明DIP诱导的这些区域特异性变化的机制，本研究对NPC1小鼠模型（NPC1 -/-）海马和小脑中的基因和蛋白进行了多组学分析。我们的研究结果显示，DIP在蛋白质水平上显著影响海马的各种通路，但在基因或蛋白质水平上对小脑的通路没有显著影响。有趣的是，给予DIP的Npc1-/-小鼠海马中受影响最大的通路是与cGMP-PKG激活和线粒体功能相关的通路。我们的结果为在其他神经退行性疾病的实验模型中测试DIP铺平了道路，比如阿尔茨海默病，它同样以海马和线粒体功能障碍为特征。

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引用次数: 0

Shen-Xiong-Tong-Mai granule suppresses nerve cell apoptosis to ameliorate ischemic stroke via activating PI3K/Akt signaling pathway 参雄通脉颗粒通过激活PI3K/Akt信号通路抑制神经细胞凋亡，改善缺血性脑卒中。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2026-01-01 DOI: 10.1016/j.brainresbull.2025.111694

Fang Yang , Yujia Zhong , Xuhong Yang , Weihong Li , Yang Zhang

Background

Ischemic stroke (IS) is a common subtype of stroke in China, accounting for 60 %-80 % of all stroke cases. Shen-Xiong-Tong-Mai granule (SXTMG) is one of the commonly used herbal medicine formulas in TCM. The present work aimed to explore the predominant active substances and molecular mechanisms underlying SXTMG against IS.

Methods

IS animal model and cell model were constructed using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) methods, respectively. The SXTMG and IS targets were predicted using four databases. UPLC/MS analysis was employed to identify the active compounds of SXTMG. The pathway changes were detected using western blot and immunofluorescence staining.

Results

Firstly, SXTMG significantly reduced the ischemic area, brain edema, and nerve function injury of MCAO rats, exhibiting crucial anti-IS effects. Totally 22 active compounds were identified in SXTMG based on HPLC-MS/MS results. After bioinformatics analysis, 89 common targets were identified, which were significantly enriched in pathways including apoptosis pathway and PI3K/Akt signaling. Finally, in vitro experiments indicated that SXTMG treatment significantly inhibited the OGD/R HT22 cell apoptosis and activated the PI3K/Akt signaling in OGD/R HT22 cells.

Conclusion

SXTMG possessed promising protective effects against IS through triggering PI3K/Akt signaling to suppress nerve cell apoptosis.

背景：缺血性脑卒中（Ischemic stroke， IS）是中国常见的脑卒中亚型，占所有脑卒中病例的60%-80%。参雄通脉颗粒（SXTMG）是中医常用的中药配方之一。本工作旨在探讨SXTMG抗IS的主要活性物质和分子机制。方法：采用大脑中动脉闭塞（MCAO）法和氧-葡萄糖剥夺/再氧化（OGD/R）法分别建立IS动物模型和细胞模型。使用四个数据库预测SXTMG和IS目标。采用超高效液相色谱/质谱联用技术对SXTMG的活性成分进行鉴定。western blot和免疫荧光染色检测通路变化。结果：首先，SXTMG显著减少MCAO大鼠的缺血面积、脑水肿和神经功能损伤，具有重要的抗is作用。通过HPLC-MS/MS分析，共鉴定出22种有效成分。经生物信息学分析，共鉴定出89个共同靶点，这些靶点在凋亡通路和PI3K/Akt信号通路中均显著富集。最后，体外实验表明，SXTMG可显著抑制OGD/R HT22细胞凋亡，激活OGD/R HT22细胞中PI3K/Akt信号通路。结论：SXTMG通过触发PI3K/Akt信号抑制神经细胞凋亡，对IS具有良好的保护作用。

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引用次数: 0