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Engrailed1 in Parvalbumin-Positive Neurons Regulates Eye-Specific Retinogeniculate Segregation and Visual Function parvalbuin阳性神经元中的Engrailed1调节眼睛特异性视网膜原环分离和视觉功能。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-20 DOI: 10.1002/jnr.70007
Yuqing Chen, Chengyong Jiang, Biao Yan, Jiayi Zhang

Homeobox transcription factor Engrailed1 (En1) is expressed in the ectoderm and mediates the establishment of retinotectal topography, but its role in eye-specific retinogeniculate segregation and visual function remains unclear. Parvalbumin (PV) neurons, which are widely distributed in the visual pathway, play a crucial role in visual development and function. In this study, we conditionally knocked out En1 gene in PV neurons and found an expansion of the ipsilateral eye projection, while no significant effects were observed in the contralateral eye projection. Additionally, we observed a decrease in the number of PV neurons in PV-Cre:En1fl/fl mice, accompanied by an increased level of cleaved caspase-3 in PV neurons. Furthermore, the genetic ablation of PV neurons in the retina through intraocular AAV-DIO-Caspase3 injection in PV-Cre mice was sufficient to disrupt retinogeniculate segregation. Finally, we observed that PV-Cre:En1fl/fl mice exhibited enhanced visual depth perception in the visual cliff test. These results demonstrate that En1 in PV neurons participates in eye-specific retinogeniculate segregation through cell survival and regulates binocular vision.

同源盒转录因子Engrailed1 (Homeobox transcription factor Engrailed1, En1)在外胚层表达,介导视网膜顶地形的建立,但其在人眼特异性视网膜环分离和视觉功能中的作用尚不清楚。小白蛋白(PV)神经元广泛分布于视觉通路中,在视觉发育和功能中起着至关重要的作用。在本研究中,我们有条件地敲除PV神经元中的En1基因,发现同侧眼投射扩大,而对侧眼投射无明显影响。此外,我们观察到PV- cre:En1fl/fl小鼠PV神经元数量减少,同时PV神经元中cleaved caspase-3水平升高。此外,通过眼内注射AAV-DIO-Caspase3对PV- cre小鼠视网膜PV神经元的基因消融足以破坏视网膜原环分离。最后,我们观察到PV-Cre:En1fl/fl小鼠在视觉悬崖测试中表现出增强的视觉深度感知。这些结果表明PV神经元中的En1通过细胞存活参与眼特异性视网膜原环分离并调节双眼视觉。
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引用次数: 0
An Open-Source Tool for Investigation of Differential RNA Expression Between Spinal Cord Cells of Male and Female Mice 一个研究雌雄小鼠脊髓细胞差异RNA表达的开源工具。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-14 DOI: 10.1002/jnr.70008
Justin Bellavance, Laurence S. David, Michael E. Hildebrand

Chronic pain is a highly debilitating condition that differs by type, prevalence, and severity between men and women. To uncover the molecular underpinnings of these differences, it is critical to analyze the transcriptomes of spinal cord pain-processing networks for both sexes. Despite several recently published single-nucleus RNA-sequencing (snRNA-seq) studies on the function and composition of the mouse spinal cord, a gene expression analysis investigating the differences between males and females has yet to be performed. Here, we combined data from three different large-scale snRNA-seq studies, which used sex-identified adult mice. Using SeqSeek, we classified more than 37,000 unique viable cells within predicted cell types with the use of machine learning. We then utilized DESeq2 to identify significant differentially expressed genes (DEGs) between males and females in a variety of cell populations, including superficial dorsal horn (SDH) neurons. We found a large number of DEGs between males and females in all cells, in neurons, and in SDH neurons of the mouse spinal cord, with a greater level of differential expression in inhibitory SDH neurons compared to excitatory SDH neurons. The results of these analyses are available on an open-source web-app: https://justinbellavance.shinyapps.io/snRNA_Visualization/. Lastly, we used gene set enrichment analysis to identify sex-enriched pathways from our previously identified DEGs. Through this, we have identified specific genetic players within the rodent spinal cord that diverge between males and females, which may underlie reported sex differences in spinal nociceptive mechanisms and pain processing.

慢性疼痛是一种极易使人衰弱的疾病,其类型、发病率和严重程度在男性和女性之间存在差异。要揭示这些差异的分子基础,分析男女脊髓疼痛处理网络的转录组至关重要。尽管最近发表了几项关于小鼠脊髓功能和组成的单核 RNA 序列(snRNA-seq)研究,但研究雌雄差异的基因表达分析尚未进行。在这里,我们综合了三项不同的大规模 snRNA-seq 研究的数据,这些研究使用了性别鉴定的成年小鼠。利用 SeqSeek,我们通过机器学习将 37,000 多个独特的存活细胞归入预测的细胞类型。然后,我们利用 DESeq2 在各种细胞群(包括背角浅层 (SDH) 神经元)中鉴定了雌雄之间显著的差异表达基因 (DEG)。我们在小鼠脊髓的所有细胞、神经元和 SDH 神经元中发现了大量雌雄差异表达基因,与兴奋性 SDH 神经元相比,抑制性 SDH 神经元的差异表达水平更高。这些分析结果可在开源网络应用程序 https://justinbellavance.shinyapps.io/snRNA_Visualization/ 上获得。最后,我们利用基因组富集分析,从先前确定的 DEGs 中识别出性别丰富的通路。通过这种方法,我们确定了啮齿类动物脊髓中雌雄之间存在差异的特定遗传参与者,这可能是脊髓痛觉机制和疼痛处理中性别差异的基础。
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引用次数: 0
Anxiety-Like Behaviors in Mice Unmasked: Revealing Sex Differences in Anxiety Using a Novel Light-Heat Conflict Test 揭露小鼠的焦虑样行为:使用一种新的光-热冲突测试揭示焦虑的性别差异。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-09 DOI: 10.1002/jnr.70002
Sydney E. Lee, Sung-Hoon Park, John C. Aldrich, Laura K. Fonken, Andrew D. Gaudet

Anxiety and chronic pain afflict hundreds of millions worldwide. Anxiety and pain are more prevalent in females compared to males. Unfortunately, robust sex differences in human anxiety are not recapitulated in rodent tests, and results from rodent pain studies frequently fail to translate clinically. Therefore, there is a need to develop tests that reflect the differential salience of anxiety or pain-related stimuli between the sexes. Accordingly, here we introduce the Thermal Increments Dark–Light (TIDAL) conflict test. The TIDAL test places an anxiety-relevant stimulus (dark vs. illuminated chamber) in conflict with a heat-related stimulus (incrementally heated vs. isothermic chamber); mice freely explore both apparatus chambers. Here, we aim to determine whether the TIDAL conflict test reveals in mice underappreciated sex differences in anxiety and/or heat sensitivity. We establish in four distinct experiments that females on the TIDAL conflict test persist substantially longer on the dark-heated plate, suggesting that female mice exhibit elevated anxiety-like behavior. Mice more strongly prefer the heated-dark plate on the TIDAL conflict test compared to control thermal place preference with both chambers illuminated. We also reveal that an anxiety-relieving drug, paroxetine, reduces mouse preference for the heating dark plate, supporting the validity of the TIDAL test. Therefore, our new TIDAL conflict test reliably unmasks the relative salience of anxiety (vs. heat sensitivity): mice that are female exhibit robust anxiety-like behaviors not consistently observed in classical tests. Future studies should incorporate TIDAL and other conflict tests to better understand rodent behavior and to identify mechanisms underlying anxiety and pain.

焦虑和慢性疼痛折磨着全世界数亿人。焦虑和疼痛在女性中比男性更普遍。不幸的是,在啮齿动物的实验中,人类焦虑的强烈性别差异并没有重现,啮齿动物疼痛研究的结果经常不能转化为临床。因此,有必要开发一种测试方法,以反映男女之间焦虑或疼痛相关刺激的不同显著性。因此,本文介绍了热增量暗光冲突测试。潮汐测试将与焦虑相关的刺激(黑暗与明亮的房间)与热相关的刺激(渐进加热与等温的房间)相冲突;老鼠可以自由地探索两个仪器室。在这里,我们的目的是确定潮汐冲突测试是否揭示了小鼠在焦虑和/或热敏性方面被低估的性别差异。我们在四个不同的实验中发现,在潮汐冲突测试中,雌性老鼠在黑暗加热的盘子上坚持的时间更长,这表明雌性老鼠表现出更高的焦虑样行为。在潮汐冲突实验中,小鼠对加热暗板的偏好比两室均有照明的热板的偏好更强烈。我们还发现,一种缓解焦虑的药物帕罗西汀(paroxetine)降低了小鼠对加热暗板的偏好,支持了TIDAL测试的有效性。因此,我们新的潮汐冲突测试可靠地揭示了焦虑(相对于热敏性)的相对显著性:雌性小鼠表现出强烈的焦虑样行为,这在经典测试中并不一致。未来的研究应纳入潮汐和其他冲突测试,以更好地了解啮齿动物的行为,并确定焦虑和疼痛的潜在机制。
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引用次数: 0
Correction to “What Do Brain Oscillations Tell About the Human Sense of Smell?” 更正 "大脑振荡对人类嗅觉有何启示?
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-09 DOI: 10.1002/jnr.70009

Mignot, C., Weise, S., Podlesek, D., Leonhardt, G., Bensafi, M., & Hummel, T. (2024). What do brain oscillations tell about the human sense of smell? Journal of Neuroscience Research, 102, e25335. https://doi.org/10.1002/jnr.25335

In Figure 1, some of the labels in the panel summarizing the different brain structures involved in smell processing were incorrectly placed.

The corrected figure and caption appear below.

We apologize for the error.

米诺特,C,怀斯,S,波德莱塞克,D,莱昂哈特,G,本萨菲,M, &;汉梅尔,T.(2024)。关于人类的嗅觉,大脑振荡告诉了我们什么?神经科学进展,2009,35(2):357 - 357。https://doi.org/10.1002/jnr.25335In图1,面板上的一些标签,总结了不同的大脑结构参与嗅觉处理的位置不正确。更正后的数字和标题如下所示。我们为这个错误道歉。
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引用次数: 0
Neurologic Music Therapy's Impact on Neurological Disorders 神经音乐疗法对神经系统疾病的影响
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-03 DOI: 10.1002/jnr.70000
Yaming Wei, Zhen Qiao

Neurologic music therapy (NMT) represents a groundbreaking, interdisciplinary approach that combines the therapeutic properties of music with neuroscientific principles to treat a range of neurological and psychiatric conditions. This interdisciplinary approach, increasingly recognized in clinical and research settings, leverages advances in neuroimaging to explore how music affects the structure and activity of the brain. This review provides an in-depth exploration of the multifaceted effects of NMT on brain function, highlighting its role in promoting neuroplastic changes and enhancing cognitive, emotional and motor functions in diverse patient groups. This review consolidates current knowledge on NMT and provides insights into how music affects brain structure and function and the mechanisms of action. The article then discusses the application and research results of NMT in various diseases such as stroke, Alzheimer's disease and Parkinson's disease. Its potential in personalizing therapeutic interventions and its ability to improve treatment access and effectiveness in various settings are highlighted.

神经音乐疗法(NMT)代表了一种开创性的跨学科方法,将音乐的治疗特性与神经科学原理相结合,以治疗一系列神经和精神疾病。这种跨学科的方法在临床和研究环境中越来越得到认可,它利用神经影像学的进步来探索音乐如何影响大脑的结构和活动。这篇综述深入探讨了NMT对脑功能的多方面影响,强调了它在促进不同患者群体的神经可塑性改变和增强认知、情绪和运动功能方面的作用。这篇综述巩固了目前关于NMT的知识,并提供了音乐如何影响大脑结构和功能以及作用机制的见解。然后讨论了NMT在脑卒中、阿尔茨海默病、帕金森病等多种疾病中的应用和研究成果。它在个性化治疗干预方面的潜力及其在各种环境中改善治疗可及性和有效性的能力得到了强调。
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引用次数: 0
Mild Traumatic Brain Injury Is Associated With Increased Thalamic Subregion Volume in the Subacute Period Following Injury 轻度创伤性脑损伤与损伤后亚急性期丘脑亚区体积增加有关
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-03 DOI: 10.1002/jnr.70004
Maggie E. Baird, Richard Beare, Marc L. Seal, Joseph Yuan-Mou Yang, Jacqueline F. I. Anderson

Structural vulnerability of the thalamus remains underinvestigated in mild traumatic brain injury (mTBI), and few studies have addressed its constituent nuclei using robust segmentation methods. This study aimed to investigate thalamic subnuclei volume in the subacute period following mTBI. Trauma control (TC) and mTBI patients aged 18–60 years old completed a magnetic resonance imaging (MRI) protocol including both high resolution structural (T1w) and diffusion-weighted sequences at 6–12 weeks following injury (mean: 57 days; SD 11). Each thalamus was segmented into its constituent subnuclei, which were grouped into eight lateralized subregions. Volumes of the subregions were calculated. Neurite Orientation Dispersion and Density (NODDI) maps with parameters optimized for gray matter were computed for the same subregions. Group differences in subregion volumes and NODDI parameters were investigated using Bayesian linear modeling, with age, sex, and estimated intracranial volume included as covariates. Comparisons of mTBI (n = 39) and TC (n = 28) groups revealed evidence of relatively increased gray matter volume in the mTBI group for the bilateral medial and right intralaminar subregions (BF10 > 3). Of the subregions which showed volume differences, there was no evidence for differences in NODDI metrics between groups. This study demonstrates that in the subacute period following mTBI, there is evidence of increased volume in specific thalamic subregions. Putative mechanisms underpinning the increased volume observed here are disordered remyelination or myelin debris yet to be cleared.

在轻度创伤性脑损伤(mTBI)中,丘脑的结构脆弱性仍未得到充分研究,并且很少有研究使用稳健的分割方法来处理其组成核。本研究旨在探讨mTBI后亚急性期丘脑亚核体积的变化。18-60岁的创伤控制(TC)和mTBI患者在损伤后6-12周(平均:57天;SD 11)。每个丘脑被分割成其组成的亚核,这些亚核被分成8个侧化亚区。计算了分区域的体积。在相同的子区域中,计算了针对灰质优化参数的神经突取向弥散和密度(NODDI)图。采用贝叶斯线性模型,以年龄、性别和估计颅内容积为协变量,研究子区域体积和NODDI参数的组间差异。mTBI组(n = 39)和TC组(n = 28)的比较显示,mTBI组双侧内侧和右侧板间亚区(BF10 > 3)的灰质体积相对增加。在显示体积差异的次区域中,没有证据表明组间NODDI指标存在差异。本研究表明,在mTBI后的亚急性期,有证据表明特定丘脑次区域的体积增加。此处观察到的体积增加的推测机制是髓鞘再生紊乱或髓鞘碎片尚未清除。
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引用次数: 0
Aberrant Dynamic Network Connectivity Changes in Comorbid Depression and Overweight/Obesity: Insights From the Triple Network Model 共病抑郁症和超重/肥胖的异常动态网络连接变化:来自三重网络模型的见解
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-29 DOI: 10.1002/jnr.70001
Zhu-Qing Zhang, Dan Liao, Zhi-Peng Guo, Shuang-Shuang Song, Xue-Jun Liu

The interaction between major depressive disorder (MDD) and overweight/obesity has received considerable attention owing to its widespread occurrence and the intricate biopsychological implications involved. Despite extensive research, the neural mechanisms underlying these comorbid conditions, particularly in terms of functional network connectivity (FNC), are still not well understood. This study aimed to clarify these mechanisms by utilizing resting-state functional magnetic resonance imaging (rs-fMRI) to examine both static and dynamic FNC. We analyzed data from 57 patients with both MDD and overweight/obesity (MDD-OW), 57 MDD patients of normal weight (MDD-NW), and 44 healthy controls, using techniques such as independent component analysis, sliding window analysis, K-means clustering, and graph theory. In contrast to static FNC, which showed no significant differences, dynamic FNC analysis identified four consistent states across all participants. Both MDD groups demonstrated reduced flexibility in functional coordination among these states and decreased nodal characteristics within the salience network. Notably, the MDD-OW group displayed enhanced dynamic FNC between the default mode network (DMN) and the executive control network (ECN) during certain states, which was inversely associated with the severity of depressive symptoms. These results highlight the importance of altered dynamic connectivity patterns in individuals with MDD and concurrent overweight/obesity, especially between the DMN and ECN, suggesting their potential utility as biomarkers for depressive states. This research contributes to our understanding of how comorbid overweight/obesity affects brain network dynamics in depressive disorders and provides a basis for targeted therapeutic strategies.

重度抑郁障碍(MDD)与超重/肥胖之间的相互作用由于其广泛的发生和复杂的生物心理学影响而受到了相当大的关注。尽管进行了广泛的研究,但这些合并症的神经机制,特别是在功能性网络连接(FNC)方面,仍然没有得到很好的理解。本研究旨在通过静息状态功能磁共振成像(rs-fMRI)检查静态和动态FNC来阐明这些机制。我们使用独立成分分析、滑动窗口分析、k均值聚类和图论等技术分析了57例重度抑郁症合并超重/肥胖(MDD- ow)患者、57例体重正常的重度抑郁症患者和44例健康对照者的数据。与静态FNC相比,动态FNC分析在所有参与者中发现了四种一致的状态。两个MDD组在这些状态之间的功能协调灵活性降低,显著性网络中的节点特征减少。值得注意的是,在某些状态下,MDD-OW组在默认模式网络(DMN)和执行控制网络(ECN)之间表现出增强的动态FNC,这与抑郁症状的严重程度呈负相关。这些结果强调了重度抑郁症并发超重/肥胖个体动态连接模式改变的重要性,特别是在DMN和ECN之间,表明它们作为抑郁状态的生物标志物的潜在效用。这项研究有助于我们理解共病超重/肥胖如何影响抑郁症的大脑网络动力学,并为有针对性的治疗策略提供基础。
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引用次数: 0
Decreased Water Diffusivity Along the Perivascular Space in Older Adults With Poor Sleep Quality 睡眠质量差的老年人血管周围空间水分弥漫性降低
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-29 DOI: 10.1002/jnr.70005
Junko Kikuta, Koji Kamagata, Kaito Takabayashi, Yayoi Hayakawa, Toshiaki Taoka, Yuya Saito, Wataru Uchida, Sen Guo, Seina Yoshida, Keigo Yamazaki, Akihiko Wada, Hideyoshi Kaga, Yoshifumi Tamura, Ryuzo Kawamori, Hirotaka Watada, Shigeki Aoki

This study included 52 Japanese older adults with Pittsburgh Sleep Quality Index (PSQI) scores > 5 and 52 healthy controls (HCs) with PSQI score ≤ 5. Diffusion-weighted imaging (DWI) and 3D T1-weighted imaging were acquired using 3T magnetic resonance imaging. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated using preprocessed DWI. The choroid plexus volume (CPV) was calculated using FreeSurfer 6.0. The mean ALPS index and CPV were compared between the older adults with poor sleep quality (PSQ) and HCs using a general linear model, adjusted for covariates including age, sex, years of education, total intracranial volume, systolic blood pressure, hemoglobin A1c, and white matter lesion volume. We also conducted a partial correlation analysis between the mean ALPS index and CPV, Montreal Cognitive Assessment (MoCA), and PSQI scores, adjusting for all the mentioned covariates. The PSQ group had a significantly lower mean ALPS index than HCs. The mean ALPS index in the PSQ group was negatively correlated with CPV and positively correlated with the MoCA score. Therefore, older adults with PSQ may experience dysfunction in the excretory pathway of the perivascular space around the medullary veins. This impairment may be associated with an increase in CPV and cognitive dysfunction.

本研究纳入52名匹兹堡睡眠质量指数(PSQI)评分为5分的日本老年人和52名PSQI评分≤5分的健康对照者。采用3T磁共振成像获取弥散加权成像(DWI)和三维t1加权成像。利用预处理后的DWI计算沿血管周围空间扩散张量图像分析(DTI-ALPS)指数。使用FreeSurfer 6.0计算脉络膜丛体积(CPV)。采用一般线性模型比较睡眠质量差的老年人(PSQ)和hc的平均ALPS指数和CPV,校正协变量包括年龄、性别、受教育年限、总颅内容积、收缩压、血红蛋白A1c和白质病变体积。我们还进行了平均ALPS指数与CPV、蒙特利尔认知评估(MoCA)和PSQI评分之间的偏相关分析,并对所有上述协变量进行了调整。PSQ组的平均ALPS指数明显低于hc组。PSQ组平均ALPS指数与CPV呈负相关,与MoCA评分呈正相关。因此,患有PSQ的老年人可能在髓静脉周围的血管周围空间的排泄途径中出现功能障碍。这种损伤可能与CPV增加和认知功能障碍有关。
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引用次数: 0
Efficacy of Low-Dose Ketamine and Propofol in the Treatment of Experimental Refractory Status Epilepticus on Male Rats 小剂量氯胺酮和丙泊酚治疗雄性大鼠实验性难治性癫痫状态的疗效
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-25 DOI: 10.1002/jnr.25393
Gaye Boztepe Yılmaz, Kemal Tolga Saraçoğlu, Uğur Aykın, Metehan Akça, Cumaali Demirtaş, Ayten Saraçoğlu, Mehmet Yıldırım

Refractory status epilepticus (RSE) is a condition with serious mortality and morbidity rate, resistant to benzodiazepine and second-line antiepileptic drugs. This study aimed to electrophysiologically investigate the combination of NMDA receptor antagonist ketamine and GABAergic agent propofol in an RSE model induced by lithium-pilocarpine in male Sprague–Dawley rats. Seventy-two male Sprague–Dawley rats were divided into nine groups. The RSE model was induced by subcutaneous injection of lithium-CI (5 mEq/kg) and intraperitoneal injection of pilocarpine-HCl (320 mg/kg), after implanting tripolar EEG electrode. Ketamine (30, 60, and 90 mg/kg), propofol (20, 40, and 80 mg/kg), and combinations of both drugs (15 + 20 and 30 + 40 mg/kg) were administered intraperitoneally to animals with RSE. Video-EEG recordings were taken after inducing model and 48 h later. The efficacy of drugs was statistically evaluated based on spike frequencies (spikes/min) and amplitudes (mV). Compared to RSE group, it was determined that 30 and 60 mg/kg doses of ketamine provided effective seizure control and prevented mortality (p < 0.001), while the 90 mg/kg showed toxic effects in all animals and caused mortality. The 80 mg/kg dose of propofol provided seizure control and reduced the mortality rate to 16.7% (p < 0.001), whereas the 20 mg/kg resulted in a 100% mortality rate. The low-dose ketamine+propofol (15 + 20 mg/kg) combination provided early onset seizure control and were as effective as 80 mg/kg propofol (p < 0.05). The study concluded that in the experimental RSE model, seizure control could be achieved with low-dose combination of ketamine and propofol without the need for high doses as in monotherapy, thus preventing dose-related adverse effects.

难治性癫痫状态(RSE)是一种对苯二氮卓类药物和二线抗癫痫药物耐药的病症,死亡率和发病率都很高。本研究旨在从电生理角度研究 NMDA 受体拮抗剂氯胺酮和 GABA 能药物异丙酚在锂-匹罗卡品诱导的雄性 Sprague-Dawley 大鼠 RSE 模型中的联合应用。72 只雄性 Sprague-Dawley 大鼠被分为 9 组。在植入三极脑电图电极后,通过皮下注射锂-CI(5 mEq/kg)和腹腔注射皮洛卡品-盐酸盐(320 mg/kg)诱导 RSE 模型。给 RSE 动物腹腔注射氯胺酮(30、60 和 90 毫克/千克)、异丙酚(20、40 和 80 毫克/千克)以及这两种药物的组合(15 + 20 和 30 + 40 毫克/千克)。在诱导模型后和 48 小时后进行视频脑电图记录。根据尖峰频率(尖峰/分钟)和振幅(mV)对药物的疗效进行了统计评估。与 RSE 组相比,30 和 60 毫克/千克剂量的氯胺酮可有效控制癫痫发作并防止死亡(p < 0.001),而 90 毫克/千克剂量的氯胺酮对所有动物均有毒性作用并导致死亡。80毫克/千克剂量的异丙酚可控制癫痫发作,并将死亡率降至16.7%(p <0.001),而20毫克/千克的异丙酚则导致100%的死亡率。低剂量氯胺酮+丙泊酚(15 + 20 毫克/千克)组合可控制早期发作,其效果与 80 毫克/千克丙泊酚相当(p < 0.05)。研究得出结论,在实验性 RSE 模型中,氯胺酮和丙泊酚的低剂量组合可控制癫痫发作,而无需像单药治疗那样使用大剂量,从而避免了剂量相关的不良反应。
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引用次数: 0
Deficits in or Preservation of Basic Number Processing in Parkinson's Disease? A Registered Report 帕金森病患者基本数字处理能力的缺失或保留?注册报告。
IF 2.9 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-16 DOI: 10.1002/jnr.25397
Hannah D. Loenneker, Christina Artemenko, Klaus Willmes, Inga Liepelt-Scarfone, Hans-Christoph Nuerk

Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health care system. Until now, diagnosis of mild cognitive impairments in PD has been established based on domain-general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD-immanent deterioration of domain-general functions and domain-specific numerical areas suggests mechanisms of both primary and secondary dyscalculia. The current study systematically investigated basic number processing performance in PD patients for the first time, targeting domain-specific cognitive representations of numerosity and the influence of domain-general factors. The overall sample consisted of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients were stratified into patients with normal cognition (PD-NC) or mild cognitive impairment (level I-PD-MCI based on cognitive screening). Basic number processing was assessed using transcoding, number line estimation, and (non-) symbolic number magnitude comparison tasks. Discriminant analysis was employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants were subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Results indicate a profile of preserved (verbal representation) and impaired (magnitude representation, place × value activation) function in PD-MCI, hinting at basal ganglia dysfunction affecting numerical cognition in PD. Numerical deficits could not be explained by domain-general cognitive impairments, so that future research needs to incorporate domain-specific tasks of sufficient difficulty.

帕金森病(PD)等神经退行性疾病对患者、护理人员和医疗保健系统产生了巨大影响。迄今为止,帕金森病轻度认知障碍的诊断一直是基于执行功能、注意力或工作记忆等领域性功能。然而,临床实践中观察到的具体数字缺陷尚未得到系统研究。帕金森氏症引起的领域性一般功能和特定领域数字领域的退化表明了原发性和继发性计算障碍的机制。本研究首次系统地调查了帕金森氏症患者的基本数字处理能力,目标是特定领域的数字认知表征以及领域一般因素的影响。总体样本包括根据共识指南确诊为帕金森病的患者和健康对照组。帕金森病患者被分为认知正常(PD-NC)或轻度认知障碍(基于认知筛查的I级-PD-MCI)患者。使用转码、数列估计和(非)符号数字大小比较任务评估基本数字处理能力。为了评估基本数字处理任务能否区分健康对照组和帕金森病组,我们采用了判别分析。所有参与者都接受了全面的数字和神经心理测试,以及社会人口学和临床测量。结果表明,在帕金森氏综合症-多发性硬化症患者中,存在功能保留(言语表征)和功能受损(幅度表征、位置 × 值激活)的情况,这暗示基底神经节功能障碍会影响帕金森氏综合症患者的数字认知。一般领域的认知障碍无法解释数字缺陷,因此未来的研究需要纳入具有足够难度的特定领域任务。
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Journal of Neuroscience Research
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