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Effects of a 12-Week Periodized Resistance Training Program on Resting Brain Activity and Cerebrovascular Function: A Nonrandomized Pilot Trial. 12周周期抗阻训练计划对静息脑活动和脑血管功能的影响:一项非随机试验。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221119441
Timothy R Macaulay, Amy Hegarty, Lirong Yan, Dominique Duncan, Judy Pa, Jason J Kutch, Marianna La Rocca, Christianne J Lane, E Todd Schroeder

Resistance training is a promising strategy to promote healthy cognitive aging; however, the brain mechanisms by which resistance training benefits cognition have yet to be determined. Here, we examined the effects of a 12-week resistance training program on resting brain activity and cerebrovascular function in 20 healthy older adults (14 females, mean age 69.1 years). In this single group clinical trial, multimodal 3 T magnetic resonance imaging was performed at 3 time points: baseline (preceding a 12-week control period), pre-intervention, and post-intervention. Along with significant improvements in fluid cognition (d = 1.27), 4 significant voxelwise clusters were identified for decreases in resting brain activity after the intervention (Cerebellum, Right Middle Temporal Gyrus, Left Inferior Parietal Lobule, and Right Inferior Parietal Lobule), but none were identified for changes in resting cerebral blood flow. Using a separate region of interest approach, we provide estimates for improved cerebral blood flow, compared with declines over the initial control period, in regions associated with cognitive impairment, such as hippocampal blood flow (d = 0.40), and posterior cingulate blood flow (d = 0.61). Finally, resistance training had a small countermeasure effect on the age-related progression of white matter lesion volume (rank-biserial = -0.22), a biomarker of cerebrovascular disease. These proof-of-concept data support larger trials to determine whether resistance training can attenuate or even reverse salient neurodegenerative processes.

抗阻训练是促进健康认知衰老的有效策略;然而,抗阻训练对认知有益的大脑机制尚未确定。在这里,我们研究了12周的阻力训练计划对20名健康老年人(14名女性,平均年龄69.1岁)静息脑活动和脑血管功能的影响。在这项单组临床试验中,在3个时间点进行多模态3t磁共振成像:基线(12周对照期之前)、干预前和干预后。随着流体认知的显著改善(d = 1.27),干预后发现静息脑活动减少的4个显著体向簇(小脑、右侧颞中回、左侧顶叶下小叶和右侧顶叶下小叶),但未发现静息脑血流量的变化。使用单独的感兴趣区域方法,我们提供了脑血流量改善的估计,与初始控制期间的下降相比,在与认知障碍相关的区域,如海马血流量(d = 0.40)和后扣带血流量(d = 0.61)。最后,阻力训练对脑白质病变体积(脑白质病变体积是脑血管疾病的一种生物标志物)的年龄相关进展有较小的抑制作用(rank-双序列= -0.22)。这些概念验证数据支持更大规模的试验,以确定阻力训练是否可以减轻甚至逆转显著的神经退行性过程。
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引用次数: 0
Harnessing Spinal Interneurons for Spinal Cord Repair. 利用脊髓中间神经元修复脊髓。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221101607
Lyandysha V Zholudeva, Michael A Lane

Interest in spinal interneurons (SpINs), their heterogeneity in the naive spinal cord and their varying responses to central nervous system injury or disease has been steadily increasing. Our recent review on this topic highlights the vast phenotypic heterogeneity of SpINs and the efforts being made to better identify and classify these neurons. As our understanding of SpIN phenotype, connectivity, and neuroplastic capacity continues to expand, new therapeutic targets are being revealed and novel treatment approaches developed to harness their potential. Here, we expand on that initial discussion and highlight how SpINs can be used to develop advanced, targeted cellular therapies and personalized medicines.

对脊髓中间神经元(spin)、它们在幼稚脊髓中的异质性以及它们对中枢神经系统损伤或疾病的不同反应的兴趣一直在稳步增加。我们最近对这一主题的综述强调了旋转神经元的巨大表型异质性以及为更好地识别和分类这些神经元所做的努力。随着我们对SpIN表型、连通性和神经可塑性的理解不断扩大,新的治疗靶点正在被发现,新的治疗方法正在开发,以利用它们的潜力。在这里,我们扩展了最初的讨论,并强调了如何使用自旋来开发先进的靶向细胞疗法和个性化药物。
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引用次数: 1
Brain Networks of Connectionally Unique Basolateral Amygdala Cell Types 连接独特的基底外侧杏仁核细胞类型的脑网络
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221080175
Houri Hintiryan, Hong-wei Dong
Different brain regions structurally interconnected through networks regulate behavior output. Therefore, understanding the functional organization of the brain in health and disease necessitates a foundational anatomic roadmap to its network organization. To provide this to the research community, our lab has systematically traced thousands of pathways in the mouse brain and has applied computational measures to determine the network architecture of major brain systems. Toward this effort, the brain-wide networks of the basolateral amygdalar complex (BLA) were recently generated. The data revealed uniquely connected cell types within the same BLA nucleus that were constituents of distinct neural networks. Here, we elaborate on how these connectionally unique BLA cell types fit within the larger cortico-basal ganglia and limbic networks that were previously described by our team. The significance and utility of high quality, detailed anatomic data is also discussed.
通过网络在结构上相互连接的不同大脑区域调节行为输出。因此,了解大脑在健康和疾病中的功能组织需要一个网络组织的基础解剖路线图。为了向研究界提供这一点,我们的实验室系统地追踪了小鼠大脑中的数千条通路,并应用计算方法确定了主要大脑系统的网络结构。为此,最近产生了基底外侧杏仁核复合体(BLA)的全脑网络。数据揭示了同一BLA核内独特连接的细胞类型,这些细胞类型是不同神经网络的组成部分。在这里,我们详细阐述了这些连接独特的BLA细胞类型如何适应我们团队之前描述的更大的皮质基底神经节和边缘网络。还讨论了高质量、详细的解剖数据的重要性和实用性。
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引用次数: 2
Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA 蛋白质网络分析揭示了ALS和SMA失调过程的功能连通性
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221087740
S. Kubinski, P. Claus
Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases which are characterized by the loss of motoneurons within the central nervous system. SMA is a monogenic disease caused by reduced levels of the Survival of motoneuron protein, whereas ALS is a multi-genic disease with over 50 identified disease-causing genes and involvement of environmental risk factors. Although these diseases have different causes, they partially share identical phenotypes and pathomechanisms. To analyze and identify functional connections and to get a global overview of altered pathways in both diseases, protein network analyses are commonly used. Here, we used an in silico tool to test for functional associations between proteins that are involved in actin cytoskeleton dynamics, fatty acid metabolism, skeletal muscle metabolism, stress granule dynamics as well as SMA or ALS risk factors, respectively. In network biology, interactions are represented by edges which connect proteins (nodes). Our approach showed that only a few edges are necessary to present a complex protein network of different biological processes. Moreover, Superoxide dismutase 1, which is mutated in ALS, and the actin-binding protein profilin1 play a central role in the connectivity of the aforementioned pathways. Our network indicates functional links between altered processes that are described in either ALS or SMA. These links may not have been considered in the past but represent putative targets to restore altered processes and reveal overlapping pathomechanisms in both diseases.
脊髓性肌萎缩症(SMA)和肌萎缩侧索硬化症(ALS)是神经退行性疾病,其特征是中枢神经系统内运动神经元的丧失。肌萎缩侧索硬化症是一种由运动神经元蛋白存活水平降低引起的单基因疾病,而肌萎缩侧索硬化症是一种多基因疾病,已确定的致病基因超过50个,并涉及环境危险因素。虽然这些疾病有不同的病因,但它们部分具有相同的表型和病理机制。为了分析和确定功能联系,并获得这两种疾病中改变的途径的总体概况,蛋白质网络分析是常用的。在这里,我们使用了一个计算机工具来测试参与肌动蛋白细胞骨架动力学、脂肪酸代谢、骨骼肌代谢、应激颗粒动力学以及SMA或ALS危险因素的蛋白质之间的功能关联。在网络生物学中,相互作用由连接蛋白质(节点)的边表示。我们的方法表明,只需要几个边缘来呈现不同生物过程的复杂蛋白质网络。此外,在ALS中发生突变的超氧化物歧化酶1 (Superoxide dismutase 1)和肌动蛋白结合蛋白(actin-binding protein profin1)在上述通路的连接中起着核心作用。我们的网络表明在ALS或SMA中描述的改变过程之间的功能联系。这些联系在过去可能没有被考虑到,但代表了恢复改变过程的假定目标,并揭示了两种疾病中重叠的病理机制。
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引用次数: 4
Commentary: How Do Microglia Regulate Neural Circuit Connectivity and Activity in the Adult Brain? 评论:小胶质细胞如何调节成人大脑中的神经回路连接和活动?
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055211071124
Yong-Jun Liu, Kim N Green, Todd C Holmes, Xiangmin Xu

Microglia are the primary immune cells in CNS. Recent work shows that microglia are also essential for proper brain development through synaptic pruning and remodeling during early life development. But the question of whether and how microglia regulate synaptic connectivity in the adult brain remains open. Our recently published study provides new insights into the functional roles of microglia in the adult mouse brain. We find that chronic depletion of microglia via CSF1R inhibitors in the visual cortex in adult mice induces a dramatic increase in perineuronal nets, and enhances neural activities of both excitatory neurons and parvalbumin interneurons. These findings highlight new potential therapeutic avenues to enhance adult neural plasticity by manipulating microglia.

小胶质细胞是中枢神经系统的初级免疫细胞。最近的研究表明,在生命早期发育过程中,小胶质细胞也通过突触修剪和重塑对大脑的正常发育至关重要。但是关于小胶质细胞是否以及如何调节成人大脑中的突触连接的问题仍然没有定论。我们最近发表的研究为小胶质细胞在成年小鼠大脑中的功能作用提供了新的见解。我们发现,成年小鼠视觉皮层中的CSF1R抑制剂慢性消耗小胶质细胞可诱导神经元周围网络的急剧增加,并增强兴奋性神经元和小白蛋白中间神经元的神经活动。这些发现强调了通过操纵小胶质细胞来增强成人神经可塑性的新的潜在治疗途径。
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引用次数: 1
Test-Retest Reliability and Agreement of Single Pulse Transcranial Magnetic Stimulation (TMS) for Measuring Activity in Motor Cortex in Patients With Acute Ischemic Stroke. 单脉冲经颅磁刺激(TMS)测量急性缺血性脑卒中患者运动皮质活动的重测信度和一致性。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221145002
Busk Henriette, Nilsen Marianne, Pedersen Julie Rønne, Kristensen Malene Glavin, Kjær Troels Wesenberg, Skou Søren Thorgaard, Wienecke Troels

Background: Transcranial magnetic stimulation (TMS) is often used to examine neurophysiology. We aimed to investigate the inter-rater reliability and agreement of single pulse TMS in hospitalised acute ischemic stroke patients.

Methods: Thirty-one patients with first-time acute ischemic stroke (median age 72 (IQR 64-75), 35% females) underwent TMS motor threshold (MT) assessment in 4 muscles bilaterally, conducted by 1 of 2 physiotherapists. Test-retest reliability was evaluated using a two-way random effects model (2,1) absolute agreement-type Interclass Correlation Coefficient (ICC). Standard Error of Measurement (SEM) and Smallest Detectable Change (SDC) were used to evaluate agreement.

Results: Reliability, SEM, and SDC of TMS was found to be moderate in right opponens pollicis (0.78 [CI 95% 0.55-0.89], SEM: 4.51, SDC: 12.51), good in right vastus medialis and tibial anterior (0.88 [CI 95% 0.72-0.96], SEM: 2.89, SDC: 8.01 and 0.88 [CI 95% 0.76-0.94], SEM: 2.88, SDC: 7.98 respectively), and excellent in right and left biceps brachii (0.98 [CI 95% 0.96-0.99], SEM: 1.79 SDC: 4.96, and 0.94 [CI 95% 0.89-0.97], SEM: 2.17 SDC: 6.01), opponens pollicis (0.92 [CI 95% 0.83-0.96], SEM: 2.68 SDC: 8.26, vastus medialis (0.92 [CI 95% 0.84-0.96], SEM: 2.87 SDC: 7.95), and tibial anterior (0.93 [CI 95% 0.86-0.96], SEM: 2.51 SDC: 6.95).

Conclusion: The TMS demonstrated moderate to excellent inter-rater reliability confirming the ability of these measures to reliably discriminate between individuals in the current study sample. Improvements of less than 4.96 to 12.51 could be a result of measurement error and may therefore not be considered a true change.

背景:经颅磁刺激(TMS)常用于神经生理学检查。我们的目的是研究急性缺血性脑卒中住院患者单脉冲经颅磁刺激的可靠性和一致性。方法:31例首次急性缺血性脑卒中患者(中位年龄72岁(IQR 64-75),女性35%),由2名物理治疗师中的1名进行双侧4块肌肉的TMS运动阈值(MT)评估。采用双向随机效应模型(2,1)绝对一致性类间相关系数(ICC)评估重测信度。使用测量标准误差(SEM)和最小可检测变化(SDC)来评估一致性。结果:可靠性、SEM和提交的经颅磁刺激在正确的对向肌温和全身(0.78 (95% CI 0.55 - -0.89),扫描电镜:4.51,署:12.51),在右股内侧肌和胫骨前(0.88 (95% CI 0.72 - -0.96),扫描电镜:2.89,署:8.01和0.88 (95% CI 0.76 - -0.94),扫描电镜:2.88,署:7.98),和优秀的左、右肱二头肌(0.98 (95% CI 0.96 - -0.99),扫描电镜:1.79署:4.96,和0.94 (95% CI 0.89 - -0.97),扫描电镜:2.17署:6.01),对全身(0.92 (95% CI 0.83 - -0.96),扫描电镜:2.68 SDC: 8.26,股内侧肌(0.92 [CI 95% 0.84-0.96], SEM: 2.87 SDC: 7.95),胫骨前肌(0.93 [CI 95% 0.86-0.96], SEM: 2.51 SDC: 6.95)。结论:经颅磁刺激表现出中等至优异的评分者间信度,证实了这些措施在当前研究样本中可靠区分个体的能力。小于4.96到12.51的改进可能是测量误差的结果,因此可能不被认为是真正的变化。
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引用次数: 1
A Tailored Music-Motor Therapy and Real-Time Biofeedback Mobile Phone App (‘GotRhythm’) to Promote Rehabilitation Following Stroke: A Pilot Study 定制的音乐-运动疗法和实时生物反馈手机应用程序(“gorhythm”)促进中风后康复:一项试点研究
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221100587
Katherine Hankinson, A. Shaykevich, A. Vallence, J. Rodger, Michael A. Rosenberg, C. Etherton-Beer
Background: Stroke persists as an important cause of long-term disability world-wide with the need for rehabilitation strategies to facilitate plasticity and improve motor function in stroke survivors. Rhythm-based interventions can improve motor function in clinical populations. This study tested a novel music-motor software application ‘GotRhythm’ on motor function after stroke. Methods: Participants were 22 stroke survivors undergoing inpatient rehabilitation in a subacute stroke ward. Participants were randomised to the GotRhythm intervention (combining individualised music and augmented auditory feedback along with wearable sensors to deliver a personalised rhythmic auditory stimulation training protocol) or usual care. Intervention group participants were offered 6-weeks of the GotRhythm intervention, consisting of a supervised 20-minute music-motor therapy session using GotRhythm conducted 3 times a week for 6 weeks. The primary feasibility outcomes were adherence to the intervention and physical function (change in the Fugl-Meyer Assessment of Motor Recovery score) measured at baseline, after 3-weeks and at end of the intervention period (6-weeks). Results: Three of 10 participants randomised to the intervention did not receive any of the GotRhythym music-motor therapy. Of the remaining 7 intervention group participants, only 5 completed the 3-week mid-intervention assessment and only 2 completed the 6-week post-intervention assessment. Participants who used the intervention completed 5 (IQR 4,7) sessions with total ‘dose’ of the intervention of 70 (40, 201) minutes. Conclusion: Overall, adherence to the intervention was poor, highlighting that application of technology assisted music-based interventions for stroke survivors in clinical environments is challenging along with usual care, recovery, and the additional clinical load.
背景:中风仍然是世界范围内长期残疾的重要原因,需要康复策略来促进中风幸存者的可塑性和改善运动功能。心律干预可以改善临床人群的运动功能。本研究测试了一种新的音乐-运动软件应用程序“gorhythm”对中风后运动功能的影响。方法:参与者是22名在亚急性中风病房接受住院康复治疗的中风幸存者。参与者被随机分配到gorhythm干预组(结合个性化音乐和增强听觉反馈以及可穿戴传感器来提供个性化节奏听觉刺激训练方案)或常规护理组。干预组参与者接受为期6周的gotrhym干预,包括使用gotrhym进行监督的20分钟音乐运动治疗,每周进行3次,持续6周。主要可行性结果是在基线、3周后和干预期结束(6周)时测量的干预依从性和身体功能(Fugl-Meyer运动恢复评分的变化)。结果:随机分配到干预组的10名参与者中有3名没有接受任何gotrhyrhythm音乐运动疗法。在其余7名干预组参与者中,只有5名完成了3周的干预中期评估,只有2名完成了6周的干预后评估。使用干预的参与者完成了5个疗程(IQR 4,7),干预的总“剂量”为70(40,201)分钟。结论:总体而言,干预的依从性较差,突出表明在临床环境中应用技术辅助的基于音乐的干预对中风幸存者的日常护理,康复和额外的临床负荷具有挑战性。
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引用次数: 7
Thanks to Reviewers 感谢审稿人
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2021-01-01 DOI: 10.1177/26331055211000487
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引用次数: 0
Hearing Impaired Participants Improve More Under Envelope-Transcranial Alternating Current Stimulation When Signal to Noise Ratio Is High. 当信噪比高时,经颅交流电刺激对听力受损者的改善效果更好。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2021-01-01 DOI: 10.1177/2633105520988854
Jules Erkens, Michael Schulte, Matthias Vormann, Anna Wilsch, Christoph S Herrmann

An issue commonly expressed by hearing aid users is a difficulty to understand speech in complex hearing scenarios, that is, when speech is presented together with background noise or in situations with multiple speakers. Conventional hearing aids are already designed with these issues in mind, using beamforming to only enhance sound from a specific direction, but these are limited in solving these issues as they can only modulate incoming sound at the cochlear level. However, evidence exists that age-related hearing loss might partially be caused later in the hearing processes due to brain processes slowing down and becoming less efficient. In this study, we tested whether it would be possible to improve the hearing process at the cortical level by improving neural tracking of speech. The speech envelopes of target sentences were transformed into an electrical signal and stimulated onto elderly participants' cortices using transcranial alternating current stimulation (tACS). We compared 2 different signal to noise ratios (SNRs) with 5 different delays between sound presentation and stimulation ranging from 50 ms to 150 ms, and the differences in effects between elderly normal hearing and elderly hearing impaired participants. When the task was performed at a high SNR, hearing impaired participants appeared to gain more from envelope-tACS compared to when the task was performed at a lower SNR. This was not the case for normal hearing participants. Furthermore, a post-hoc analysis of the different time-lags suggest that elderly were significantly better at a stimulation time-lag of 150 ms when the task was presented at a high SNR. In this paper, we outline why these effects are worth exploring further, and what they tell us about the optimal tACS time-lag.

助听器使用者经常表达的一个问题是在复杂的听力场景中难以理解语音,即当语音与背景噪音一起呈现或在有多个说话者的情况下。传统的助听器在设计时已经考虑到这些问题,使用波束形成只能增强来自特定方向的声音,但这些在解决这些问题上是有限的,因为它们只能在耳蜗水平上调制传入的声音。然而,有证据表明,与年龄相关的听力损失可能部分是在听力过程的后期引起的,因为大脑处理速度变慢,效率降低。在这项研究中,我们测试了是否有可能通过改善语音的神经跟踪来改善皮质水平的听力过程。将目标句子的语音包转化为电信号,经颅交流电刺激(tACS)刺激到老年受试者的大脑皮层。我们比较了2种不同的信噪比(SNRs)和5种不同的声音呈现和刺激延迟(50 ~ 150 ms),以及老年正常听力和老年听力受损参与者的效果差异。当任务在高信噪比下执行时,听力受损的参与者似乎比在低信噪比下执行任务时从包膜- tacs中获得更多。对于听力正常的参与者来说,情况并非如此。此外,对不同滞后时间的事后分析表明,当任务以高信噪比呈现时,老年人在150ms的刺激滞后时间下表现明显更好。在本文中,我们概述了为什么这些效应值得进一步探索,以及它们告诉我们的关于最佳tACS时滞的信息。
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引用次数: 1
Effects of Tacrolimus and Other Immune Targeting Compounds on Binge-Like Ethanol Drinking in High Drinking in the Dark Mice. 他克莫司和其他免疫靶向化合物对深色小鼠高饮水中Binge样乙醇饮酒的影响。
IF 2.9 Q2 NEUROSCIENCES Pub Date : 2020-11-25 eCollection Date: 2020-01-01 DOI: 10.1177/2633105520975412
Kolter B Grigsby, Antonia M Savarese, Pamela Metten, Barbara J Mason, Yuri A Blednov, John C Crabbe, Angela R Ozburn

High Drinking in the Dark (HDID-1) mice represent a unique genetic risk model of binge-like drinking and a novel means of screening potential pharmacotherapies to treat alcohol use disorders (AUDs). We tested the effects of tacrolimus (0, 0.5, 1, and 2 mg/kg), sirolimus (0, 5, 10, and 20 mg/kg), palmitoylethanolamide (PEA; 0, 75, 150, and 225 mg/kg), and secukinumab (0, 5, 20, and 60 mg/kg) on binge-like ethanol intake (2-day, "Drinking in the Dark" [DID]) and blood alcohol levels (BALs) in HDID-1 mice. Tacrolimus reduced ethanol intake and BALs. Tacrolimus had no effect on water intake, but reduced saccharin intake. There was no effect of sirolimus, PEA, or secukinumab on ethanol intake or BALs. These results compare and contrast with previous work addressing these compounds or their targeted mechanisms of action on ethanol drinking, highlighting the importance of screening a wide range of models and genotypes to inform the role of neuroimmune signaling in AUDs.

在黑暗中大量饮酒(HDID-1)小鼠代表了一种独特的类似狂饮的遗传风险模型,也是筛选治疗酒精使用障碍(AUD)的潜在药物疗法的新方法。我们测试了他克莫司(0、0.5、1和2 mg/kg)、西罗莫司(0、5、10和20 mg/kg)、棕榈酰乙醇酰胺(PEA;0、75、150和225 mg/kg)和secukinumab(0、5、20和60 mg/kg)和HDID-1小鼠的血液酒精水平(BALs)。他克莫司减少了乙醇摄入和BAL。他克莫司对水分摄入没有影响,但减少了糖精的摄入。西罗莫司、PEA或secukinumab对乙醇摄入或BALs没有影响。这些结果与之前针对这些化合物或其对乙醇饮用的靶向作用机制的研究进行了比较和对比,强调了筛选广泛的模型和基因型以了解神经免疫信号在AUD中的作用的重要性。
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引用次数: 0
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