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An ALS-associated mutant SOD1 protein can be eliminated in microglia culture by selective autophagy als相关的SOD1突变蛋白可以通过选择性自噬在小胶质细胞培养中消除。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-27 Epub Date: 2026-01-22 DOI: 10.1016/j.neuroscience.2026.01.017
Kumiko Murakami , Norihiro Sudou , Atushi Kurata , Motoko Kawaguchi-Niida
The acquired toxicity of the familial amyotrophic lateral sclerosis (ALS)-associated mutant Zn-superoxide dismutase 1 (SOD1) protein has been implicated in motoneuron death, and cytosolic aggregates or inclusions have been observed in the cytoplasm of motoneurons, astrocytes, and neuronal axons but not in that of microglia. This study elucidates the mechanisms by which mutant SOD1 does not aggregate in and is cleared by microglia. We generated pcDNA3-Venus-tagged SOD1 constructs: wild-type SOD1 and mutant SOD1 were used as controls, and the A4V, D90A, and G93A SOD1 mutants were used as disease-related constructs; these plasmids were introduced into the Ra2 microglia line for subsequent evaluation. In spinal cords collected from postsymptomatic G93A mice, very little aggregation of the mutant SOD1 protein was detected in microglia, consistent with previous reports. Our new findings, which were based on immunohistochemical, Western blot, and enzyme immunoassay analyses, revealed that the protein expression of mutant SOD1 in microglia is significantly lower than that of wild-type SOD1. Furthermore, we observed the recovery of mutant SOD1 protein levels in autophagy suppression experiments and its colocalization with WDFY3, a selective autophagy-related protein. These in vitro results demonstrate that only the mutant SOD1 protein (i.e., not wild-type SOD1) is degraded by selective autophagy. Furthermore, we found that both wild-type and mutant SOD1 are secreted directly from microglia. These findings provide an opportunity to elucidate the precise mechanism through which microglia manage mutant SOD1 proteins during the pathological process of ALS and are likely to lead to improvements in ALS treatment strategies.
家族性肌萎缩性侧索硬化症(ALS)相关突变体zn -超氧化物歧化酶1 (SOD1)蛋白的获得性毒性与运动神经元死亡有关,在运动神经元、星形胶质细胞和神经元轴突的细胞质中观察到胞质聚集体或包涵体,但在小胶质细胞中没有观察到。这项研究阐明了突变SOD1不聚集在小胶质细胞中并被小胶质细胞清除的机制。我们生成了pcdna3 - venus标记的SOD1构建体:野生型SOD1和突变型SOD1作为对照,A4V、D90A和G93A SOD1突变体作为疾病相关构建体;这些质粒被引入Ra2小胶质细胞系进行后续评价。在症状后的G93A小鼠脊髓中,在小胶质细胞中检测到很少的SOD1突变蛋白聚集,与先前的报道一致。我们的新发现,基于免疫组织化学,Western blot和酶免疫分析,显示突变型SOD1在小胶质细胞中的蛋白表达明显低于野生型SOD1。此外,我们在自噬抑制实验中观察到突变体SOD1蛋白水平的恢复及其与选择性自噬相关蛋白WDFY3的共定位。这些体外实验结果表明,只有突变型SOD1蛋白(即,不是野生型SOD1)被选择性自噬降解。此外,我们发现野生型和突变型SOD1都直接从小胶质细胞分泌。这些发现为阐明小胶质细胞在ALS病理过程中管理突变SOD1蛋白的确切机制提供了机会,并可能导致ALS治疗策略的改进。
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引用次数: 0
TLR2 regulation of NF-κB and NLRP3-driven pyroptosis in Alzheimer’s disease TLR2调节NF-κB和nlrp3驱动的阿尔茨海默病焦亡。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-27 Epub Date: 2026-01-23 DOI: 10.1016/j.neuroscience.2026.01.026
Lijun Zhang , Shuo Wang , Yongkun Gui , Dongli Li , Kunyan Li , Yayu Wang , Yuming Xu
Although upregulation of toll-like receptor 2 (TLR2) excessively activates pro-inflammatory microglia through Aβ peptides, it remains unclear whether TLR2 regulates neuronal pyroptosis via the NF-κB/NLRP3 pathway in Alzheimer’s disease (AD). We assessed TLR2 expression in peripheral blood from clinical samples and employed SH-SY5Y cells for initial screening. AD pathology was simulated by Aβ1-42 stimulation, and pathway regulatory relationships were dissected through TLR2 knockdown, NF-κB overexpression, and NLRP3 activation experiments. APP/PS1 mice were treated with sh-TLR2. Results demonstrated that high TLR2 expression activated the NF-κB/NLRP3 pathway and promoted pyroptosis, while TLR2 silencing suppressed Aβ1-42-driven pyroptosis in SH-SY5Y cells by inhibiting this pathway. NF-κB overexpression or NLRP3 activation partially reversed the protective effect of TLR2 silencing. In vivo experiments confirmed the role of TLR2 knockdown in AD mice. Thus, this study revealed that TLR2 drives neuronal pyroptosis via the NF-κB/NLRP3 pathway, providing a novel therapeutic target for AD. These findings complement existing microglia-centered TLR2 research and broadens the understanding of neuroinflammatory regulation. However, SH-SY5Y cells differ from primary neurons in maturity, which may limit mechanistic extrapolation. Further validation in induced pluripotent stem cells-derived primary neurons or humanized mouse models will enhance the clinical translational potential of these findings.
虽然toll样受体2 (TLR2)的上调通过Aβ肽过度激活促炎小胶质细胞,但TLR2是否通过NF-κB/NLRP3通路调节阿尔茨海默病(AD)的神经元焦亡尚不清楚。我们评估了临床样本外周血中TLR2的表达,并使用SH-SY5Y细胞进行初步筛选。通过a - β1-42刺激模拟AD病理,通过TLR2敲低、NF-κB过表达、NLRP3激活实验解剖通路调控关系。应用sh-TLR2处理APP/PS1小鼠。结果表明,TLR2的高表达激活了NF-κB/NLRP3通路,促进了SH-SY5Y细胞的焦亡,而TLR2的沉默通过抑制该通路抑制了a β1-42驱动的SH-SY5Y细胞的焦亡。NF-κB过表达或NLRP3激活部分逆转了TLR2沉默的保护作用。体内实验证实了TLR2敲低在AD小鼠中的作用。因此,本研究揭示了TLR2通过NF-κB/NLRP3通路驱动神经元焦亡,为AD的治疗提供了新的靶点。这些发现补充了现有的以小胶质细胞为中心的TLR2研究,拓宽了对神经炎症调节的理解。然而,SH-SY5Y细胞在成熟时与原代神经元不同,这可能限制了机制外推。在诱导多能干细胞衍生的原代神经元或人源化小鼠模型中进一步验证将增强这些发现的临床转化潜力。
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引用次数: 0
Experimentally induced fatigue and motor learning: A scoping review 实验诱导疲劳和运动学习:范围综述。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-27 Epub Date: 2026-01-28 DOI: 10.1016/j.neuroscience.2026.01.030
Bahram Ghafari Goushe , Layale Youssef , Thomas Mangin , Denis Arvisais , Jason L. Neva , Benjamin Pageaux
The literature on the effect of fatigue on motor learning is limited and marked by inconsistent findings. This scoping review aimed to explore the available knowledge on the effects of fatigue induced by physical and cognitive exertion on motor learning, and to compile and understand how it is studied. A comprehensive search strategy using relevant index terms and keywords was conducted across MEDLINE, EMBASE, SPORTDiscus, Web of Science, PsycINFO, CINAHL, ERIC, and Dissertations & Theses Global. Twenty-five studies met the inclusion criteria. The findings revealed considerable inconsistencies in how fatigue and motor learning were defined and measured. None of the studies examined the effect of fatigue induced by combined physical and cognitive exertion, and only 7 studies investigated fatigue induced by cognitive exertion. Acuity tasks were the most frequently used to assess motor learning, employed in 14 studies. Notably, all participants were between 16.5 and 31 years of age, and reporting of key demographic and physiological characteristics such as sex, gender, physical activity level, and body mass index was inconsistent or absent. This review highlights the need for comprehensive definitions of both fatigue and motor learning to improve consistency and reproducibility across studies. Given the limited research on the effects of fatigue induced by cognitive and combined physical and cognitive exertion, future studies should prioritize using these experimental manipulations. Also, future studies should diversify the motor learning tasks used in research to allow both direct and conceptual replication. Additionally, broader age ranges and comprehensive participant profiling should be prioritized.
关于疲劳对运动学习的影响的文献是有限的,并且以不一致的发现为标志。本综述旨在探讨体力和认知消耗引起的疲劳对运动学习影响的现有知识,并汇编和了解其研究方式。在MEDLINE、EMBASE、SPORTDiscus、Web of Science、PsycINFO、CINAHL、ERIC和disserts&theses Global等平台上使用相关索引词和关键词进行了全面的搜索策略。25项研究符合纳入标准。研究结果显示,疲劳和运动学习的定义和测量存在相当大的不一致性。没有一项研究调查了体力和认知联合消耗引起的疲劳的影响,只有7项研究调查了认知消耗引起的疲劳。在14项研究中,敏锐度任务是评估运动学习最常用的方法。值得注意的是,所有参与者的年龄都在16.5到31 岁之间,关键的人口统计学和生理特征(如性别、性别、身体活动水平和体重指数)的报告不一致或缺失。这篇综述强调需要对疲劳和运动学习进行全面的定义,以提高研究的一致性和可重复性。鉴于目前对认知及体能与认知联合运动引起的疲劳影响的研究有限,未来的研究应优先使用这些实验操作。此外,未来的研究应该使研究中使用的运动学习任务多样化,以允许直接和概念复制。此外,应优先考虑更广泛的年龄范围和全面的参与者分析。
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引用次数: 0
Altered cerebral morphometry and individual-based morphological brain network in children with beta-thalassaemia major 重度地中海贫血儿童脑形态测量学改变和基于个体的脑形态网络。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-27 Epub Date: 2026-01-29 DOI: 10.1016/j.neuroscience.2026.01.036
Yaowen Li , Zhuoshuo Li , Shumin Xu , Xinyi Liu , Sixi Liu , Xiaodong Wang , Mengting Liu , Hongwu Zeng
Beta-thalassemia major (TM) is a severe genetic blood disorder that frequently leads to cognitive impairments in pediatric patients, yet its neurological impact remains insufficiently explored. This study investigates alterations in cerebral gray matter morphology and brain network topology in children with TM and their associations with cognitive performance. High-resolution brain MRI data were processed using FreeSurfer to extract cortical morphological features, from which individual-based Morphological Brain Networks (MBNs) were constructed based on vertex-wise similarity across gray matter regions. A cohort of 27 children with TM and 40 age-matched healthy controls underwent structural network analysis, standardized cognitive assessments, and comprehensive blood testing, including evaluations of hemoglobin and iron concentrations. Results revealed marked structural disruptions in the motor and temporal cortices of TM patients. Network-level analysis further identified topological abnormalities within fronto-parietal regions, suggesting altered structural connectivity patterns that may underlie observed cognitive deficits. Notably, iron overload was significantly correlated with both regional brain changes and impaired network organization, indicating a plausible mechanistic link between systemic iron dysregulation and neural dysfunction. These findings underscore the neurological vulnerability of children with TM and illuminate the structural basis of their cognitive challenges. The study highlights the need to integrate neuroimaging biomarkers with clinical hematological profiles to better understand TM’s effects on brain development. Future work should aim to expand these findings through longitudinal designs and larger samples to inform early neurocognitive interventions and optimize treatment strategies for this vulnerable population.
乙型地中海贫血(TM)是一种严重的遗传性血液疾病,经常导致儿科患者认知障碍,但其对神经系统的影响仍未得到充分探讨。本研究探讨了TM患儿脑灰质形态和脑网络拓扑结构的改变及其与认知表现的关系。使用FreeSurfer对高分辨率脑MRI数据进行处理,提取皮层形态特征,并基于灰质区域的顶点相似性构建基于个体的脑形态网络(MBNs)。27名TM儿童和40名年龄匹配的健康对照者进行了结构网络分析、标准化认知评估和全面的血液检测,包括血红蛋白和铁浓度的评估。结果显示,TM患者的运动皮层和颞叶皮层有明显的结构破坏。网络水平的分析进一步确定了额顶叶区域的拓扑异常,表明结构连接模式的改变可能是观察到的认知缺陷的基础。值得注意的是,铁超载与大脑区域变化和网络组织受损显著相关,表明系统性铁调节失调与神经功能障碍之间存在似是而非的机制联系。这些发现强调了TM儿童的神经脆弱性,并阐明了他们认知挑战的结构基础。该研究强调需要将神经成像生物标志物与临床血液学资料结合起来,以更好地了解TM对大脑发育的影响。未来的工作应该旨在通过纵向设计和更大的样本来扩展这些发现,为早期神经认知干预提供信息,并优化针对这一弱势群体的治疗策略。
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引用次数: 0
δ-catenin haploinsufficiency is sufficient to alter behaviors and glutamatergic synapses in mice δ-连环蛋白单倍不足足以改变小鼠的行为和谷氨酸能突触。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-27 Epub Date: 2026-02-04 DOI: 10.1016/j.neuroscience.2026.01.044
Emma S. Hinchliffe , Victoria Aragon , Van T. Mai , Swapna A. Shah , Rahmi Lee , Jyothi Arikkath , Seonil Kim
δ-catenin (also known as CTNND2) functions as an anchor for the glutamatergic AMPA receptor (AMPARs) to regulate synaptic activity in excitatory synapses. Alteration in the gene coding δ-catenin has been implicated in many neurological disorders. Some of these genetic alterations exhibit a profound loss of δ-catenin functions in excitatory synapses. We have shown that δ-catenin deficiency induced by the homozygous δ-catenin knockout (KO) and autism-associated missense glycine 34 to serine (G34S) mutation significantly alters AMPAR-mediated synaptic activity in cortical neurons and disrupts social behavior in mice. Importantly, many genetic disorders are caused by haploinsufficiency. Indeed, δ-catenin haploinsufficiency contributes to severe autism and learning disabilities in humans. However, previous studies have used only homozygous δ-catenin deficiency models. Therefore, it is important to examine the effects of δ-catenin haploinsufficiency on animals’ behaviors and excitatory synapses. Here, we use heterozygous δ-catenin KO and G34S mice as a δ-catenin haploinsufficiency model to examine this idea. Multiple behavioral assays, a social behavior test, contextual fear conditioning, and an open field test, reveal that both δ-catenin KO and G34S haploinsufficiency significantly disrupt animals’ social behavior and fear learning and memory. Interestingly, only KO haploinsufficiency mice show anxiety-like behavior. A biochemical assay using brain extracts demonstrates that δ-catenin haploinsufficiency significantly affects the levels of synaptic δ-catenin and AMPARs. Our findings thus suggest that δ-catenin haploinsufficiency affects animals’ behaviors via altering glutamatergic synaptic activity.
δ-catenin(也称为CTNND2)作为谷氨酸AMPA受体(AMPARs)的锚点,调节兴奋性突触的突触活性。基因编码δ-连环蛋白的改变与许多神经系统疾病有关。其中一些遗传改变在兴奋性突触中表现出δ-连环蛋白功能的严重丧失。我们已经证明,由δ-catenin敲除(KO)和自闭症相关的错义甘氨酸34到丝氨酸(G34S)突变引起的δ-catenin缺乏显著改变了ampar介导的皮质神经元突触活性,并扰乱了小鼠的社会行为。重要的是,许多遗传疾病是由单倍功能不全引起的。事实上,δ-连环蛋白单倍体不足导致了人类严重的自闭症和学习障碍。然而,以前的研究只使用纯合子δ-catenin缺乏症模型。因此,研究δ-catenin单倍体不足对动物行为和兴奋性突触的影响具有重要意义。在这里,我们使用杂合δ-catenin KO和G34S小鼠作为δ-catenin单倍不足模型来检验这一观点。社会行为测试、情境恐惧条件反射和开放场测试等多项行为分析结果显示,δ-catenin KO和G34S单倍不足均显著干扰动物的社会行为和恐惧学习记忆。有趣的是,只有KO单倍不足小鼠表现出焦虑样行为。脑提取物的生化分析表明,δ-catenin单倍不足显著影响突触δ-catenin和ampar的水平。因此,我们的研究结果表明δ-连环蛋白单倍不足通过改变谷氨酸突触活性来影响动物的行为。
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引用次数: 0
Profiling metabotropic glutamate receptor 7 expression in Rett syndrome: consequences for pharmacotherapy 代谢性谷氨酸受体7在Rett综合征中的表达分析:药物治疗的后果。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-27 Epub Date: 2026-01-30 DOI: 10.1016/j.neuroscience.2026.01.040
Sheryl Anne D. Vermudez , Geanne A. Freitas , Mackenzie Smith , Rocco G. Gogliotti , Colleen M. Niswender
Rett syndrome (RTT) is caused by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) transcription factor. RTT patients undergo a developmental regression between 6–18 months of age, resulting in the presentation of symptoms including repetitive behaviors, seizures, autistic-like features, and apneas. We have reported that levels of metabotropic glutamate receptor 7 (mGlu7) are significantly decreased in brain samples from RTT patients carrying truncation mutations in the MECP2 gene. Additionally, we have identified decreases in Mecp2+/- mice and demonstrated that administration of a positive allosteric modulator (PAM) with activity at mGlu7 corrected deficits in cognitive, social, and respiratory domains. Here, we expanded our studies to a larger cohort of RTT samples covering a range of mutations and evaluated expression of the three widely expressed group III mGlu receptors (mGlu4,7 and 8). We found significant decreases in mGlu7, but not mGlu4 or mGlu8, mRNA expression across this larger cohort; additionally, we identified a previously unknown correlation in the expression of mGlu4 and mGlu8 in human brain samples. Stratification of RTT patients into those with classically severe versus mild MECP2 pathogenic mutations revealed statistically significant decreases in mGlu7 expression only in patients with mutations associated with severe symptoms. To establish whether target disruption is required for efficacy, we administered the PAM VU0422288 to mice modeling the mild R306C mutation (Mecp2R306C/+) and found a significant reduction in apneas. These results provide the first evidence of potentially broad utility for mGlu7 PAMs in reducing apneas across the RTT spectrum.
Rett综合征(RTT)是由x -连锁甲基- cpg结合蛋白2 (MeCP2)转录因子突变引起的。RTT患者在6-18 月龄之间经历发育倒退,导致出现重复行为、癫痫发作、自闭症样特征和呼吸暂停等症状。我们报道了携带MECP2基因截断突变的RTT患者的脑样本中代谢性谷氨酸受体7 (mGlu7)的水平显著降低。此外,我们已经发现Mecp2+/-小鼠的减少,并证明给予具有mGlu7活性的阳性变构调节剂(PAM)可以纠正认知、社交和呼吸领域的缺陷。在这里,我们将研究扩展到一个更大的RTT样本队列,涵盖了一系列突变,并评估了三种广泛表达的III组mGlu受体(mGlu4、7和8)的表达。在这个更大的队列中,我们发现mGlu7的mRNA表达显著降低,但mGlu4或mGlu8的mRNA表达没有显著降低;此外,我们还发现了人脑样本中mGlu4和mGlu8表达的未知相关性。将RTT患者分为典型重度和轻度MECP2致病突变,结果显示,mGlu7表达仅在与严重症状相关的突变患者中有统计学意义的降低。为了确定是否需要破坏靶标才能有效,我们将PAM VU0422288给予轻度R306C突变(Mecp2R306C/+)的小鼠,发现呼吸暂停显著减少。这些结果为mGlu7 pam在减少RTT频谱呼吸暂停方面的潜在广泛应用提供了第一个证据。
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引用次数: 0
Acquisition and extinction of conditioned action tendencies in motor cortex. 运动皮层条件动作倾向的习得与消失。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-21 DOI: 10.1016/j.neuroscience.2026.03.025
Rachael Yu, Dominic M D Tran, Cameron K Phan, Evan J Livesey, Justin A Harris

Routine behaviours can become habitual, persisting even when task goals have changed. Thus, it is important that we understand how these behaviours, and their underlying neurophysiological mechanisms, can be modulated. In the current experiment, participants were trained across multiple sessions to associate specific stimuli on a computer monitor with a key-press response. This learned action tendency, developed through repeated stimulus-response pairings, was then reduced using an extinction procedure in which the stimulus was repeatedly presented but no response was to be made. The underlying neurophysiological mechanisms of the learned response and its subsequent extinction were investigated using motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) delivered to the primary motor cortex (M1). We observed that exposure to the conditioned stimulus increased corticospinal excitability in M1, and this effect was modulated by the extinction procedure. We also found evidence that stimulation of M1 using TMS can trigger the release of a cued motor response that may have otherwise been withheld. This novel finding supports the notion that an associated motor plan is generated automatically in M1 when perceiving a conditioned stimulus associated with responding. Implications of these results in the context of conditioned action tendencies are discussed.

常规行为可以变成习惯,即使任务目标改变了也会持续下去。因此,了解这些行为及其潜在的神经生理机制是如何被调节的是很重要的。在目前的实验中,参与者接受了多次训练,将电脑显示器上的特定刺激与按键反应联系起来。这种习得的行为倾向是通过反复的刺激-反应配对发展起来的,然后通过反复出现刺激但不做出反应的消退过程来减少。利用经颅磁刺激(TMS)对初级运动皮层(M1)激发的运动诱发电位(MEP)来研究习得反应及其随后消退的潜在神经生理机制。我们观察到,暴露于条件刺激增加了M1的皮质脊髓兴奋性,这种效应是由消退过程调节的。我们还发现有证据表明,使用经颅磁刺激刺激M1可以触发一种暗示的运动反应的释放,否则这种反应可能会被抑制。这一新颖的发现支持了这样一种观点,即当感知到与反应相关的条件刺激时,M1会自动产生相关的运动计划。这些结果在条件行动倾向的背景下的含义进行了讨论。
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引用次数: 0
Therapeutic efficacy of engineered exosomes in Alzheimer's disease: A systematic review and meta-analysis of preclinical animal models. 工程外泌体治疗阿尔茨海默病的疗效:临床前动物模型的系统回顾和荟萃分析。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-20 DOI: 10.1016/j.neuroscience.2026.03.019
An Li, Weijun Peng, Beibei Wu, Chuyu Li, Jingjing Yang

Engineered exosomes are modified extracellular vesicles designed to enhance targeting and cargo delivery, and they have been proposed as a therapeutic strategy for Alzheimer's disease. We systematically reviewed preclinical animal studies evaluating engineered exosomes, synthesized evidence from comparisons with disease models and with natural exosomes, and reported the study in accordance with the PRISMA 2020 checklist. Outcomes included spatial learning and memory assessed by the Morris water maze, amyloid beta pathology, tau phosphorylation, and neuroinflammatory markers. Random effects meta-analyses suggested that engineered exosomes improved Morris water maze performance and reduced amyloid beta burden and pro-inflammatory cytokines compared with natural exosomes, whereas evidence regarding tau phosphorylation was limited and largely qualitative, and the overall certainty of evidence was low to very low. These findings support further investigation of engineered exosomes, but conclusions should be interpreted cautiously until confirmed by rigorously designed and blinded preclinical studies and clinical trials with standardized protocols.

工程外泌体是经过修饰的细胞外囊泡,旨在增强靶向性和货物递送,它们已被提出作为阿尔茨海默病的治疗策略。我们系统地回顾了评估工程外泌体的临床前动物研究,从与疾病模型和天然外泌体的比较中合成了证据,并根据PRISMA 2020清单报告了这项研究。结果包括通过Morris水迷宫、β淀粉样蛋白病理、tau磷酸化和神经炎症标志物评估的空间学习和记忆。随机效应荟萃分析表明,与天然外泌体相比,工程外泌体改善了莫里斯水迷宫的表现,减少了淀粉样蛋白β负担和促炎细胞因子,而关于tau磷酸化的证据有限且主要是定性的,证据的总体确定性很低。这些发现支持对工程外泌体的进一步研究,但结论应谨慎解释,直到经过严格设计和盲法临床前研究和标准化方案的临床试验证实。
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引用次数: 0
The effects of acute psychosocial stress on binge urges, inhibitory control, negative urgency and eating pathology in Binge Eating Disorder. 急性心理社会压力对暴食症患者暴食冲动、抑制控制、负性急迫性和进食病理的影响。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-20 DOI: 10.1016/j.neuroscience.2026.03.024
S L Brassard, K Punia, M Laliberte, H Liu, K M Lucibello, S Potter, I M Balodis

Stress is frequently reported as a trigger for binge episodes, yet it remains unclear how subjective and physiological stress responses interact with cognitive and affective mechanisms to increase binge eating risk. The present study investigated the effects of acute psychosocial stress on binge urges, focusing on the role of state- and trait-level vulnerabilities. Twenty-eight individuals with BED were randomized to either a Stress condition (n = 14) or No-Stress condition (n = 14). Following an acute psychosocial stressor, participants completed the Stop-Signal Task to behaviourally assess inhibitory control. Self-reported mood, binge urge ratings and saliva samples for stress biomarker detection were collected at three timepoints throughout the experimental session. Results demonstrated that acute psychosocial stress elicited marked increases in total mood disturbance, without corresponding physiological stress responses and significantly impaired inhibitory control. Notably, only subjective stress responses were associated with greater binge urges, whereas physiological stress responses were not. This dissociation highlights subjective stress reactivity as a clinically meaningful mechanism of risk in BED, underscoring the potential value of interventions that target stress perception and regulation to reduce binge eating vulnerability.

压力经常被报道为暴食发作的触发因素,但尚不清楚主观和生理应激反应如何与认知和情感机制相互作用,从而增加暴食风险。本研究调查了急性心理社会压力对暴食冲动的影响,重点关注状态和特质层面脆弱性的作用。28名BED患者被随机分为应激组(n = 14)和无应激组(n = 14)。在急性社会心理压力源后,参与者完成了停止信号任务,以行为上评估抑制控制。在整个实验过程中,在三个时间点收集自我报告的情绪、暴食冲动评分和用于压力生物标志物检测的唾液样本。结果表明,急性社会心理应激引起总情绪障碍显著增加,而没有相应的生理应激反应和显著的抑制控制受损。值得注意的是,只有主观应激反应与更大的暴食冲动有关,而生理应激反应与之无关。这种分离强调了主观应激反应作为BED风险的临床有意义的机制,强调了针对应激感知和调节的干预措施的潜在价值,以减少暴饮暴食的脆弱性。
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引用次数: 0
MSCMH-Net: A multi-scale channel-mixing hybrid network for whole-brain segmentation. MSCMH-Net:一种用于全脑分割的多尺度信道混合网络。
IF 2.8 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-03-19 DOI: 10.1016/j.neuroscience.2026.03.022
Wanting Zhang, Jinhua Yue, Bo Liu, Fugen Zhou

Whole-brain segmentation constitutes a fundamental task in medical image analysis, providing quantitative assessment of fine-grained brain regions and serving as a cornerstone for both clinical practice and neuroscience research. Despite its importance, the task is inherently challenging given the numerous brain regions, pronounced inter-class heterogeneity, and sophisticated inter-class spatial dependencies. Accurate whole-brain segmentation requires not only precise delineation of local features but also comprehensive modeling of long-range dependencies and global contextual information. To tackle these challenges, we propose the Multi-Scale Channel-Mixing Hybrid Network (MSCMH-Net), a CNN-MLP hybrid framework integrating convolutional and MLP modules at multiple hierarchical levels. The framework leverages the strengths of CNNs to capture local features and spatial structures, while employing MLPs to model long-range dependencies and global contextual information. For integrating global and local information, a channel-mixing module incorporating an exponential moving average (EMA) fusion strategy is employed. A composite dataset of 106 brain MR scans was used, including 36 from MICCAI-2012, 30 from ADNI and 40 from OASIS. Ground truth labels were annotated and double-checked by experts. Comprehensive experiments conducted on the composite dataset validate that MSCMH-Net achieves competitive results relative to existing approaches.

全脑分割是医学图像分析的一项基本任务,它提供了细粒度脑区域的定量评估,是临床实践和神经科学研究的基石。尽管它很重要,但考虑到大脑区域众多、明显的阶级间异质性和复杂的阶级间空间依赖性,这项任务本身就具有挑战性。准确的全脑分割不仅需要精确描绘局部特征,还需要对远程依赖关系和全局上下文信息进行全面建模。为了应对这些挑战,我们提出了多尺度信道混合网络(MSCMH-Net),这是一个CNN-MLP混合框架,在多个层次上集成了卷积和MLP模块。该框架利用cnn的优势来捕获局部特征和空间结构,同时使用mlp来建模远程依赖关系和全局上下文信息。为了集成全局和局部信息,采用了一个结合指数移动平均(EMA)融合策略的信道混合模块。使用了106个脑磁共振扫描的复合数据集,其中36个来自MICCAI-2012, 30个来自ADNI, 40个来自OASIS。实地真相标签由专家进行注释和双重检查。在复合数据集上进行的综合实验验证了MSCMH-Net相对于现有方法取得了具有竞争力的结果。
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Neuroscience
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