Neuroscience最新文献_第8页

Neurodevelopmental outcomes following prenatal cannabidiol exposure in male and female Sprague Dawley rat offspring. 产前大麻二酚暴露在雄性和雌性大鼠后代中的神经发育结果。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-09 DOI: 10.1016/j.neuroscience.2025.12.018

Sarah L Baccetto, Tallan Black, Ilne L Barnard, Leah M Macfarlane, Genre B Sanfuego, Robert B Laprairie, John G Howland

Cannabis use, including among pregnant women, has increased in recent years due to legalization and other factors in several countries. Cannabidiol (CBD), one of Cannabis's main constituents, is often seen as a natural and safe substance and increasingly used for treating medical conditions such as pain, anxiety, and depression. Women report using CBD during pregnancy to alleviate pregnancy-related symptoms such as nausea, vomiting, and chronic pain. However, few studies exist in the literature regarding the consequences of prenatal CBD exposure. In this study, we treated pregnant rats with CBD (5 and 10 mg/kg; i.p.) once daily from gestational day 6 to 20 and then tracked litter health parameters and conducted neurodevelopmental behavioral tests to assess how treatment affected development. Offspring exposed to CBD prenatally weighed less on postnatal day 1 and gained less weight before weaning on postnatal day 21. Treatment with 10 mg/kg CBD decreased performance in homing behaviour. Subtle changes in righting reflex during the first postnatal week were observed in offspring of litters treated with the higher dose of CBD. These differences resolved by postnatal day 21. No significant differences in a gait test, negative geotaxis, or grip strength were noted. The present results contribute to a growing body of evidence regarding the safety of CBD use during pregnancy and suggest that pregnant people and health care professionals should be cognizant of the potential adverse outcomes of prenatal CBD exposure on growth and development.

近年来，由于一些国家的大麻合法化和其他因素，包括孕妇在内的大麻使用有所增加。大麻二酚（CBD）是大麻的主要成分之一，通常被视为一种天然安全的物质，越来越多地用于治疗疼痛、焦虑和抑郁等疾病。妇女报告说，在怀孕期间使用CBD可以缓解与怀孕有关的症状，如恶心、呕吐和慢性疼痛。然而，文献中很少有关于产前暴露于CBD的后果的研究。在这项研究中，我们从妊娠第6天至第20天每天给怀孕大鼠注射一次CBD(5和10 mg/kg； i.p.)，然后跟踪产仔健康参数并进行神经发育行为测试，以评估治疗如何影响发育。产前暴露于CBD的后代在出生后第1天体重较轻，在出生后第21天断奶前体重增加较少。10 mg/kg CBD处理降低了归巢行为的表现。在高剂量CBD处理的窝仔的后代中，观察到在出生后第一周的翻正反射的细微变化。这些差异在出生后第21天就消失了。步态测试、负地向性或握力均无显著差异。目前的研究结果为孕期使用CBD的安全性提供了越来越多的证据，并建议孕妇和卫生保健专业人员应认识到产前暴露于CBD对生长发育的潜在不良后果。

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引用次数: 0

Nitrous oxide promotes exploratory activity and stimulates neurogenesis in a male rat model of post-traumatic stress disorder 在创伤后应激障碍雄性大鼠模型中，氧化亚氮促进探索活动并刺激神经发生

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-08 DOI: 10.1016/j.neuroscience.2025.12.017

Batoul Darwish , Jad El Masri , Lina Hourieh , Ziad Nahas , Wassim Abou-Kheir , Farah Chamaa

Neurogenesis in the adult brain is a precisely regulated process that remains highly sensitive to intrinsic and extrinsic influences. Among the external factors are psychological conditions, such as post-traumatic stress disorder (PTSD), which arises after exposure to trauma such as war, accidents, violence, or natural disasters. PTSD, as well as other disorders like stress and depression, has been linked to diminished hippocampal neurogenesis. In this study, we utilized the single prolonged stress (SPS) model to induce PTSD-like behavior in male rats, demonstrating its suppressive effects on hippocampal neurogenesis and on exploratory behavior. Recent research has explored the potential of nitrous oxide gas (N2O), an anesthetic and analgesic used in medical procedures, as a potential treatment for depression. Accordingly, we propose nitrous oxide exposure as a therapeutic intervention for PTSD-like to counteract its adverse effects on neurogenesis and anxiety-related behavior. Our results showed that SPS-exposed rats exhibited reduced exploratory performance in the Y-maze test and increased anxiety behavior in the elevated plus maze. Furthermore, BrdU tracing revealed decreased neurogenesis in these rats compared to sham. Remarkably, exposure to nitrous oxide reduced anxiety-related symptoms of SPS-exposed rats and enhanced neurogenesis. This aligns with prior research, highlighting nitrous oxide as a promising therapeutic avenue for addressing PTSD and other psychological disorders. We propose nitrous oxide as a therapeutic approach for treating cognitive and anxiety-related symptoms of PTSD through its effects on hippocampal neurogenesis. However, further comprehensive research is essential to understand the potential benefits, risks and long-term impacts associated with this treatment approach.

成人大脑中的神经发生是一个精确调控的过程，对内在和外在影响保持高度敏感。外部因素包括心理状况，如创伤后应激障碍（PTSD），它是在暴露于战争、事故、暴力或自然灾害等创伤后产生的。创伤后应激障碍，以及压力和抑郁等其他疾病，都与海马神经发生减少有关。在本研究中，我们采用单次延长应激（SPS）模型诱导雄性大鼠ptsd样行为，证明其对海马神经发生和探索行为的抑制作用。最近的研究已经探索了一氧化二氮气体（N2O）作为一种医疗程序中使用的麻醉剂和止痛药的潜力，作为抑郁症的潜在治疗方法。因此，我们建议将氧化亚氮暴露作为类创伤后应激障碍的治疗干预措施，以抵消其对神经发生和焦虑相关行为的不利影响。结果表明，暴露于sps的大鼠在y型迷宫中探索性表现下降，在高架+迷宫中焦虑行为增加。此外，BrdU示踪显示，与假手术相比，这些大鼠的神经发生减少。值得注意的是，暴露于一氧化二氮减少了暴露于sps的大鼠的焦虑相关症状，并增强了神经发生。这与先前的研究一致，强调氧化亚氮是治疗创伤后应激障碍和其他心理障碍的有希望的治疗途径。我们建议通过对海马神经发生的影响，将氧化亚氮作为治疗PTSD认知和焦虑相关症状的一种治疗方法。然而，进一步的综合研究对于了解与这种治疗方法相关的潜在益处、风险和长期影响至关重要。

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引用次数: 0

The relationship between the salience network and facial emotion recognition in social anxiety disorder 社交焦虑障碍显著性网络与面部情绪识别的关系。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-08 DOI: 10.1016/j.neuroscience.2025.12.015

Kohei Kurita , Tomomi Nagano , Junbing He , Tokiko Yoshida , Koji Matsumoto , Yuka Oishi , Eiji Shimizu , Yoshiyuki Hirano

Social anxiety disorder (SAD) is thought to involve the negative evaluation of facial emotions. Although imaging studies have examined this aspect, no study has investigated the relationship between resting-state functional connectivity (rsFC) and facial emotion recognition in SAD. Hyperconnectivity in the salience network, particularly involving the anterior cingulate cortex (ACC), has been reported to be associated with facial recognition and SAD. This study aimed to identify the association between rsFC and facial emotion recognition in patients with SAD. We included 21 patients with SAD and 34 healthy controls (HCs). Participants underwent resting-state functional MRI, clinical assessment, and emotion recognition tasks (ERT). Group differences in ERT were analyzed using a two-sample t-test. rsFC focused on the ACC as the region of interest (ROI). Partial correlation analyses, adjusted for age and sex, focused on items that showed significant differences in ERT. Furthermore, we performed a partial correlation analysis between the extracted rsFC and Liebowitz Social Anxiety Scale (LSAS) total score. Patients with SAD identified significantly more disgust facial emotions (ERT-disgust) than HCs. rsFC associated with ERT disgust was identified between the ACC and the left insula in SAD. However, rsFC did not correlate with LSAS scores. Patients with SAD accurately identified disgust facial expressions compared to HCs. The rsFC associated with disgust facial expression recognition differed between patients with SAD and HCs, with the salience network playing an important role in SAD.

社交焦虑障碍（SAD）被认为与对面部情绪的负面评价有关。虽然影像学研究已经对这方面进行了研究，但还没有研究调查SAD患者静息状态功能连接（rsFC）与面部情绪识别之间的关系。据报道，突出网络的超连通性，特别是涉及前扣带皮层（ACC），与面部识别和SAD有关。本研究旨在确定SAD患者rsFC与面部情绪识别之间的关系。我们纳入了21例SAD患者和34例健康对照（hc）。参与者接受静息状态功能MRI、临床评估和情绪识别任务（ERT）。ERT的组间差异采用双样本t检验分析。rsFC将ACC作为感兴趣区域（ROI）。部分相关分析，调整了年龄和性别，集中在显示ERT显着差异的项目上。此外，我们对提取的rsFC与Liebowitz社交焦虑量表（LSAS）总分进行偏相关分析。SAD患者识别出的厌恶面部情绪（ERT-disgust）明显多于hc患者。在SAD患者的ACC和左岛之间发现了与ERT厌恶相关的rsFC。然而，rsFC与LSAS评分没有相关性。与hc相比，SAD患者准确地识别出厌恶的面部表情。与厌恶面部表情识别相关的rsFC在SAD和hc患者之间存在差异，突出网络在SAD中起重要作用。

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引用次数: 0

Visual involvement precedes motor dysfunction in experimental autoimmune encephalomyelitis: evidence from non-invasive in vivo electrophysiology and imaging 实验性自身免疫性脑脊髓炎的视觉受累先于运动功能障碍：来自非侵入性体内电生理和成像的证据

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-07 DOI: 10.1016/j.neuroscience.2025.12.016

Silvia Marenna , Elena Rossi , Valerio Castoldi , Su-Chun Huang , Chiara Malacrida , Giancarlo Comi , Letizia Leocani

The Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis is associated with abnormalities in visual (VEP) and motor (MEP) evoked potentials, together with neuroretinal thinning at optical coherence tomography (OCT). The time course of these deficits is pivotal for testing novel therapeutic strategies. Thus, VEP, MEP, and OCT were performed during the prodromal, acute, and chronic phases of EAE. A group of EAE mice were sacrificed for histological analysis at each timepoint. VEP latency delays at prodromal phases were associated with early optic nerve demyelination. OCT scans revealed subtle retinal pathology before clinical motor onset, while in the chronic phase, MEP dysfunction was detected and validated by demyelination, inflammation and axonal loss. Interestingly, VEP abnormalities appear before electrophysiological or clinical motor involvement, pointing to the relevance of neurophysiological measures to detect early subclinical demyelination, which could be a potential target of novel therapeutic approaches targeting inflammation, demyelination and neuroaxonal loss.

多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）模型与视觉（VEP）和运动（MEP）诱发电位异常以及光学相干断层扫描（OCT）神经视网膜变薄有关。这些缺陷的时间过程是测试新的治疗策略的关键。因此，在EAE的前驱、急性和慢性期进行VEP、MEP和OCT检查。在每个时间点处死一组EAE小鼠进行组织学分析。前驱期VEP潜伏期延迟与早期视神经脱髓鞘有关。OCT扫描显示，在临床运动发病前，视网膜有细微病变，而在慢性期，MEP功能障碍通过脱髓鞘、炎症和轴突丧失被检测和验证。有趣的是，VEP异常出现在电生理或临床运动参与之前，这表明神经生理指标与检测早期亚临床脱髓鞘的相关性，这可能是针对炎症、脱髓鞘和神经轴突丧失的新治疗方法的潜在靶点。

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引用次数: 0

Alarm pheromone activates posterior medial amygdala-to-bed nucleus of the stria terminalis projections in male rats 报警信息素激活雄性大鼠尾纹后内侧杏仁核到床核的投射

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-07 DOI: 10.1016/j.neuroscience.2025.12.013

Mao Kobayashi-Sakashita , Ming-Hsuan Lu , Yukari Takeuchi , Markus Fendt , Akira Uematsu , Yasushi Kiyokawa

Animals communicate using olfactory signals called pheromones. Alarm pheromones are evolutionarily conserved and alert conspecifics to danger. In rats, a mixture of hexanal and 4-methylpentanal was identified as the main component that evokes anxiety responses by activating the anterior bed nucleus of the stria terminalis (aBNST). In addition, the posteroventral medial amygdala (pvMeA) was proposed to transmit the alarm pheromone signal to the aBNST. Here, we assessed whether the binary mixture activates direct pvMeA-to-aBNST projections or indirect projections via other MeA subdivisions in male rats. In Experiment 1, we virally labeled synaptophysin either in all types of efferent projections (n = 5) or selectively in glutamatergic efferent projections (n = 5) of the pvMeA. When we observed from the main olfactory bulb to the cerebellum, both types of signals were detected across 22 regions, with the aBNST showing the highest densities of both signals. These results suggest that the pvMeA transmits direct, predominantly glutamatergic projections to the aBNST. In Experiment 2, we injected a retrograde tracer into the aBNST and observed Fos expression in response to water (n = 6) or the binary mixture (n = 7) in the medial amygdala. We found that double-labeled cells were increased only in the pvMeA and posterodorsal medial amygdala (pdMeA). These results suggest that the binary mixture activates both the pvMeA-to-aBNST and pdMeA-to-aBNST projections. Taken together, we propose that the posterior medial amygdala transmits the alarm pheromone signal to the aBNST. These findings may support efforts to improve the welfare of livestock animals.

动物通过一种叫做信息素的嗅觉信号进行交流。警报信息素在进化上是保守的，它提醒同种生物注意危险。在大鼠中，己醛和4-甲基戊醛的混合物被确定为通过激活终纹前床核（aBNST）引起焦虑反应的主要成分。此外，提出后腹侧内侧杏仁核（pvMeA）将报警信息素信号传递到aBNST。在这里，我们评估了二元混合物是否激活了雄性大鼠pvMeA-to-aBNST的直接投影或通过其他MeA细分的间接投影。在实验1中，我们在pvMeA的所有类型的传出突起（n = 5）或选择性地在谷氨酸能传出突起（n = 5）中对synaptophysin进行了病毒标记。当我们从主嗅球到小脑进行观察时，这两种信号在22个区域都被检测到，其中aBNST显示出这两种信号的最高密度。这些结果表明pvMeA将直接的，主要是谷氨酸能的投射传递给aBNST。在实验2中，我们将逆行示踪剂注射到aBNST中，观察内侧杏仁核对水（n = 6）或二元混合物（n = 7）的Fos表达。我们发现双标记细胞仅在pvMeA和后嗅侧内侧杏仁核（pdMeA）增加。这些结果表明，二元混合物激活了pvMeA-to-aBNST和pdMeA-to-aBNST的投影。综上所述，我们认为后内侧杏仁核将报警信息素信号传递给aBNST。这些发现可能支持提高牲畜福利的努力。

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引用次数: 0

Doublecortin-expressing cells are selectively altered in the piriform cortex but not in neurogenic areas of symptomatic Mecp2-heterozygous mice 双皮质素表达细胞在梨状皮质中选择性改变，而在症状性mecp2杂合小鼠的神经源性区域中不发生改变

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-07 DOI: 10.1016/j.neuroscience.2025.12.010

Rafael Esteve-Pérez , Paloma Sevilla-Ferrer , Enrique Lanuza , Vicente Herranz-Pérez , Jose V. Torres-Pérez , Carmen Agustín-Pavón

Rett Syndrome (RTT) is a neurodevelopmental disorder which mainly affects girls, leading to profound impairments in motor function, loss of speech, intellectual disability, and epilepsy, among other symptoms. Most cases are caused by mutations in the X-linked MECP2 gene, which encodes the methyl-CpG-binding protein 2 (MeCP2), an epigenetic reader with a crucial function in the regulation of neural maturation. Previously, using the marker of immature neurons doublecortin (DCX), we showed that a population of embryonic-born neurons of the piriform cortex, which experience prolonged maturation throughout life, was increased in the piriform cortex of symptomatic young adult (2 months old) Mecp2-null male mice. By contrast, these cells were not affected in age matched Mecp2-heterozygous female mice, who are pre-symptomatic at that age. To determine whether symptom onset would affect DCX-expressing neurons, in this study we analysed samples from 6 months old, symptomatic Mecp2-heterozygous female mice. Our results show a specific increase in the density of DCX-positive neurons in the piriform cortex, consistent with observations in males. However, no differences were detected in the neurogenic niches of the dentate gyrus or the ventricular-subventricular zone when compared to their wild-type controls. Further, morphological analyses of the DCX-expressing cells of the piriform cortex reveal that they are smaller and show less complex dendritic branching in mutant mice. In conclusion, our findings support a role of MeCP2 in the maturation process of the embryonic-born DCX neurons in the piriform cortex and point to region-specific alterations in neuronal maturation in RTT.

Rett综合征（RTT）是一种主要影响女孩的神经发育障碍，可导致运动功能严重受损、语言丧失、智力残疾和癫痫等症状。大多数病例是由x连锁的MECP2基因突变引起的，该基因编码甲基cpg结合蛋白2 (MECP2)， MECP2是一种表观遗传解读器，在神经成熟的调节中具有关键功能。先前，我们使用未成熟神经元双皮质素（DCX）标记物，发现在有症状的年轻成年（2个月大）mecp2缺失雄性小鼠梨状皮质中，梨状皮质中胚胎出生的神经元数量增加，这些神经元在一生中经历了长时间的成熟。相比之下，这些细胞在年龄匹配的mecp2杂合雌性小鼠中没有受到影响，这些小鼠在该年龄出现症状前。为了确定症状发作是否会影响表达dcx的神经元，在本研究中，我们分析了来自6个月大、有症状的mecp2杂合雌性小鼠的样本。我们的研究结果显示，梨状皮质中dcx阳性神经元的密度明显增加，这与男性的观察结果一致。然而，与野生型对照相比，齿状回或脑室-室下区神经源性壁龛没有发现差异。此外，对表达dcx的梨状皮质细胞的形态学分析表明，突变小鼠的梨状皮质细胞更小，树突分支更不复杂。总之，我们的研究结果支持MeCP2在梨状皮质中胚胎出生的DCX神经元成熟过程中的作用，并指出RTT中神经元成熟的区域特异性改变。

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引用次数: 0

Do sex differences influence test habituation and internal data validity in neurocognitive testing? A blinded measurement error analysis 性别差异是否影响神经认知测试的测试习惯和内部数据效度？盲法测量误差分析

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-07 DOI: 10.1016/j.neuroscience.2025.12.007

Konstantin Warneke , Manuel Oraze , Marco Herbsleb , José Afonso , Sebastian Wallot

Reliable neurocognitive assessment requires sufficient habituation to ensure that test outcomes reflect stable cognitive performance rather than learning effects. This study examined the influence of repeated testing and sex differences on the reliability and internal validity of three widely used neurocognitive tasks: the Trail Making Test, Stroop Test (Word Read and Color Read), and CRT. One hundred healthy young adults (47 men, 53 women) completed all tasks twice daily over five consecutive days. Relative and absolute reliability, as well as agreement metrics were calculated to quantify systematic and random errors. Significant within- and between-days habituation effects were observed. Reliability varied substantially: the reaction tasks showed the highest stability, followed by Stroop tasks; the Trail-Making-Test B demonstrated the lowest reproducibility. Systematic improvements were most pronounced between sessions one and two and generally stabilized after two to four days of familiarization. Sex-specific analyses revealed consistent male superiority in choice reaction performance. Sex differences in habituation were task-dependent and primarily reflected differences in adaptation rate rather than the magnitude of improvement. Across sexes, sufficient task familiarization was essential to minimize systematic and random errors. Overall reliability metrics were similar across sexes. Maximal random errors were reported in the Trail-Making-Test, contradicting unhabituated test application to track longitudinal changes or establishing valid cross-sectional analyses.

可靠的神经认知评估需要充分的习惯化，以确保测试结果反映稳定的认知表现，而不是学习效果。本研究考察了重复测试和性别差异对三种广泛使用的神经认知任务的信度和内部效度的影响：造径测试、Stroop测试（单词阅读和颜色阅读）和CRT。100名健康的年轻人（47名男性，53名女性）在连续5天内每天完成两次所有任务。计算相对和绝对可靠性，以及一致性度量来量化系统和随机误差。观察到显著的日内和日间习惯效应。可靠性差异很大：反应任务的稳定性最高，其次是Stroop任务；试制试验B重现性最低。系统的改善在第一和第二阶段之间最为明显，在两到四天的熟悉之后基本稳定下来。性别分析显示，男性在选择反应表现上始终具有优势。习惯化的性别差异是任务依赖的，主要反映了适应率的差异，而不是改善程度的差异。无论男女，充分的任务熟悉是必要的，以尽量减少系统和随机错误。总体可靠性指标在两性之间是相似的。在trail - mak- test中报告了最大的随机误差，这与不习惯的测试应用来跟踪纵向变化或建立有效的横断面分析相矛盾。

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引用次数: 0

Profiling the Braak progression in Parkinson’s disease: a transcriptomics and ML driven identification of progressive biomarker and prognostic ceRNA signature 分析帕金森病的Braak进展：转录组学和ML驱动的进行性生物标志物和预后ceRNA特征的鉴定

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-06 DOI: 10.1016/j.neuroscience.2025.12.011

Sudarshan Sarkar, Soumita Podder

Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder, is marked by dopaminergic neuron loss and α-synuclein aggregation. Although Braak staging based on Lewy body pathology stratifies disease progression, clinical variability persists. Identifying stage-specific molecular signatures is essential for developing effective progressive biomarkers. Here, we integrated midbrain transcriptomic data from microarray, bulk RNA-seq, and snRNA-seq platforms. Subsequently, to catalogue candidate biomarkers of PD progression, we employed a three-layered approach integrating Protein-protein-interaction networks, shortest-path analysis, and ModuLand-based module detection. By mapping gene interactions within and across Braak stages, we identified core module genes that influence network topology and play pivotal roles in disease advancement. Braak stage transition analysis further highlighted 66 key genes, significantly enriched in ubiquitin-mediated proteolysis, cytokine signaling, and neurodegenerative pathways. ElasticNet regression short-listed these to ten candidate biomarkers with strong predictive power (AUC ≥ 0.90), and six genes consistently showed good accuracy (AUROC > 0.75) across Random Forest, GBM, and CatBoost models. Validation with blood transcriptome data supported their utility as non-invasive biomarker. Further, survival analysis of PPMI data highlighted the prognostic significance of HSPA1B, LRRK2, and DNAJB1, identifying them as potential risk associated genes in PD. Among these, only HSPA1B yielded a competitive-endogenous-RNA network with prognostic relevance, and its differential expression between early and late PD stages further supported its role as a progressive biomarker. The key regulatory axis identified—XIST → miR-221-3p/miR-23a-5p/miR-548au-3p → HSPA1B offers both prognostic value and mechanistic insight into PD progression, with potential for early diagnosis and targeted therapy.

帕金森病（PD）是第二大最常见的神经退行性疾病，其特征是多巴胺能神经元丧失和α-突触核蛋白聚集。尽管基于路易体病理的Braak分期将疾病进展分层，但临床变异性仍然存在。识别特定阶段的分子特征对于开发有效的进行性生物标志物至关重要。在这里，我们整合了来自微阵列、散装RNA-seq和snRNA-seq平台的中脑转录组学数据。随后，为了对PD进展的候选生物标志物进行分类，我们采用了一种三层方法，将蛋白质-蛋白质相互作用网络、最短路径分析和基于moduland的模块检测结合起来。通过绘制Braak阶段内部和之间的基因相互作用图谱，我们确定了影响网络拓扑并在疾病进展中发挥关键作用的核心模块基因。Braak分期分析进一步突出了66个关键基因，这些基因在泛素介导的蛋白水解、细胞因子信号传导和神经退行性途径中显著富集。ElasticNet回归列出了10个具有强大预测能力的候选生物标志物（AUC ≥ 0.90），其中6个基因在Random Forest， GBM和CatBoost模型中一致显示出良好的准确性（AUROC > 0.75）。血液转录组数据验证支持其作为非侵入性生物标志物的效用。此外，PPMI数据的生存分析强调了HSPA1B、LRRK2和DNAJB1的预后意义，确定它们是PD的潜在风险相关基因。其中，只有HSPA1B产生了与预后相关的竞争性内源性rna网络，其在PD早期和晚期的差异表达进一步支持了其作为进行性生物标志物的作用。确定的关键调控轴- xist → miR-221-3p/miR-23a-5p/miR-548au-3p → HSPA1B提供了PD进展的预后价值和机制洞察，具有早期诊断和靶向治疗的潜力。

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引用次数: 0

Beyond brain scans: verbal memory testing as an efficient cognitive biomarker for preclinical Alzheimer’s disease 超越脑部扫描：言语记忆测试作为临床前阿尔茨海默病的有效认知生物标志物。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-05 DOI: 10.1016/j.neuroscience.2025.12.008

Odelia Elkana , Orin Segal , Iman Beheshti , for the Alzheimer’s Disease Neuroimaging Initiative

Timely and accessible tools for detecting preclinical Alzheimer’s disease (AD) are essential for early intervention, yet reliance on MRI biomarkers limits scalability. Using longitudinal data from 210 cognitively normal older adults in ADNI, we compared the predictive value of verbal episodic memory, hippocampal volume, and a visuospatial composite. Over a 7-year window, 106 participants progressed to mild cognitive impairment (MCI), while 104 remained stable. At baseline, Immediate Recall on the Rey Auditory Verbal Learning Test was the strongest predictor of progression (AUC = 0.71), outperforming hippocampal volume (AUC = 0.66) and visuospatial scores (AUC = 0.57). Longitudinal models confirmed a steeper decline in converters (p < 0.001), underscoring its sensitivity to preclinical disease dynamics. Immediate recall accurately detected subtle functional changes, achieving predictive performance highly comparable to MRI-based hippocampal measurements. Immediate Recall is brief, low-cost, and has the potential for digital adaptation, making it a scalable tool for early detection and monitoring of cognitive changes. It could be deployed online or in community-based care where advanced diagnostics are limited.

One Sentence Summary

Immediate verbal recall outperforms hippocampal volume and visuospatial measures in predicting conversion to mild cognitive impairment, offering a scalable, low-cost tool for early detection in aging populations.

及时和可获得的检测临床前阿尔茨海默病（AD）的工具对于早期干预至关重要，但依赖MRI生物标志物限制了可扩展性。利用来自210名患有ADNI的认知正常老年人的纵向数据，我们比较了言语情景记忆、海马体积和视觉空间复合的预测价值。在7年的时间窗口中，106名参与者进展为轻度认知障碍（MCI），而104名保持稳定。在基线时，雷伊听觉语言学习测试的即时回忆是最强的进步预测因子（AUC = 0.71），优于海马体积（AUC = 0.66）和视觉空间得分（AUC = 0.57）。纵向模型证实了转换器的急剧下降

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引用次数: 0

Neuroinflammation does not exacerbate post-traumatic stress-disorder (PTSD)-like brain measures or behaviour after a traumatic event in male rats 在雄性大鼠的创伤事件后，神经炎症不会加重创伤后应激障碍（PTSD）的大脑测量或行为。

IF 2.8 3区医学 Q2 NEUROSCIENCES

Neuroscience

Pub Date : 2025-12-05 DOI: 10.1016/j.neuroscience.2025.12.014

Soniya Xavier , Harith Al-Saabary , Daniel Foran , Meagan Kovatchev , Miad Almadani , Nada Almuqati , Simin Younesi , Elizabeth Verghese , Sarah J. Spencer

Post-traumatic stress disorder (PTSD) is strongly linked to neuroinflammation, with immune activation in brain regions such as the amygdala and hippocampus potentially contributing to its long-term persistence. Yet, whether neuroinflammation experienced at the time of trauma can cause, or increase the likelihood of PTSD-like symptoms and central nervous system changes developing is currently untested. If concomitant neuroinflammation exacerbates PTSD risk, treating neuroinflammation immediately after trauma could be a strategy to prevent PTSD development. This study investigated whether an immune challenge, induced by lipopolysaccharide (LPS), could exacerbate PTSD-like behaviours and brain changes following trauma induced by footshock in male rats. As expected, LPS induced transient weight loss, increased the expression of inflammation-related genes in the amygdala and hippocampus and lead to inflammatory-associated morphological changes in microglia. Although footshock led to persistent fear memory, indicated by increased freezing in the situational reminder test, LPS did not enhance the fear memory response induced by footshock. In the elevated plus maze, footshock reduced exploratory behaviour, indicating heightened anxiety, but this was also not exacerbated by LPS. Likewise, the effects of footshock on markers of neuronal health in the amygdala and hippocampus were not changed by LPS. Our data therefore suggest that a prior immune challenge with LPS does not exacerbate PTSD-like behaviours or fear memory in rats, indicating the brain is resilient against inflammation heightening trauma responses.

创伤后应激障碍（PTSD）与神经炎症密切相关，杏仁核和海马体等大脑区域的免疫激活可能会导致其长期存在。然而，创伤时经历的神经炎症是否会导致或增加ptsd样症状和中枢神经系统变化发展的可能性，目前尚未得到验证。如果伴随的神经炎症加剧了PTSD的风险，创伤后立即治疗神经炎症可能是预防PTSD发展的一种策略。本研究探讨了脂多糖（LPS）诱导的免疫刺激是否会加剧雄性大鼠足部休克后的ptsd样行为和脑变化。正如预期的那样，LPS诱导了短暂的体重减轻，增加了杏仁核和海马中炎症相关基因的表达，并导致小胶质细胞中炎症相关的形态学改变。虽然脚震导致持续恐惧记忆，但LPS并没有增强脚震引起的恐惧记忆反应。在高架加迷宫中，足震减少了探索行为，表明焦虑加剧，但LPS也没有加剧这种情况。同样，足震对杏仁核和海马体神经元健康标志物的影响也没有被LPS改变。因此，我们的数据表明，先前的LPS免疫挑战不会加剧大鼠的创伤后应激障碍样行为或恐惧记忆，这表明大脑对炎症加剧的创伤反应具有弹性。

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引用次数: 0