EXPERIMENTAL NEUROLOGY 是一本神经科学研究杂志，发表神经科学的原创研究，特别强调神经发育、再生、可塑性和移植方面的新发现。该杂志专注于研究神经系统疾病的基本机制。

Experimental Neurology is a journal dedicated to neuroscience research, publishing original studies that particularly emphasize new findings in neurodevelopment, regeneration, plasticity, and transplantation. The journal focuses on investigating the fundamental mechanisms of neurological disorders.

《Experimental Neurology》是一本专注于神经科学研究的期刊，发表原创研究，特别强调神经发育、再生、可塑性和移植方面的新发现。该期刊致力于探讨神经系统疾病的基本机制。

Experimental Neurology

Gaucher disease, the most common lysosomal storage disorder, is caused by mutations in the gene encoding the acid-β-glucosidase lysosomal hydrolase enzyme that cleaves glucocerebroside into glucose and ceramide. Reduced enzyme activity and impaired structural stability arise due to >300 known disease-causing mutations. Several of these mutations have also been associated with an increased risk of Parkinson disease (PD). Since the discovery of the acid-β-glucosidase X-ray structure, there have been major advances in our understanding of the structural properties of the protein. Analysis of specific residues has provided insight into their functional and structural importance and provided insight into the pathogenesis of Gaucher disease and the contribution to PD. Disease-causing mutations are positioned throughout the acid-β-glucosidase structure, with many located far from the active site and thus retaining some enzymatic activity however, thus far no clear relationship between mutation location and disease severity has been established. Here, we review the crystal structure of acid-β-glucosidase, while highlighting important structural aspects of the protein in detail. This review discusses the structural stability of acid-β-glucosidase, which can be altered by pH and glycosylation, and explores the relationship between known Gaucher disease and PD mutations, structural stability and disease severity.

Laura Smith

Stephen Mullin

Anthony H V Schapira

Experimental neurology

Exp Neurol

Insights into the structural biology of Gaucher disease.

深入了解戈谢病的结构生物学。

Qin Zhao

Ci Li

Yangjie Xu

Juan Zhong

Hongzhen Liu

Ying Yin

Yuan Liu

Ce Yang

Lehua Yu

Li Liu

Lu Pan

Botao Tan

Treadmill exercise supplemented by OPN promote axon regeneration through the IGF-1R/Akt/mTOR signaling pathway

补充OPN的跑步机运动通过IGF-1R/Akt/mTOR信号通路促进轴突再生

Postoperative cognitive dysfunction (POCD) is a common complication in elderly surgical patients, significantly affecting their quality of life. Dexmedetomidine (Dex), an anesthetic, has shown promise in alleviating POCD, but its underlying mechanism remains unclear. This study aims to explore how Dex improves POCD in aged rats by targeting the PINK1-mediated mitochondrial autophagy pathway, reducing caspase-1/11-GSDMD-induced hippocampal neuronal pyroptosis. Transcriptome sequencing identified 300 differentially expressed genes enriched in the mitochondrial autophagy pathway in Dex-treated POCD rat hippocampal tissue, with Pink1 as a key candidate. In a POCD rat model, Dex treatment upregulated hippocampal PINK1 expression. In vitro experiments using H19-7 rat hippocampal neurons revealed that Dex enhanced mitochondrial autophagy and suppressed neuronal pyroptosis by upregulating PINK1. Further mechanistic validation demonstrated that Dex activated PINK1-mediated mitochondrial autophagy, inhibiting caspase-1/11-GSDMD-induced neuronal pyroptosis. In vivo experiments confirmed Dex's ability to reduce caspase-1/11-GSDMD-dependent hippocampal neuronal pyroptosis and improve postoperative cognitive function in aged rats. Dexmedetomidine improves postoperative cognitive dysfunction in elderly rats by enhancing mitochondrial autophagy via PINK1 upregulation, mitigating caspase-1/11-GSDMD-induced neuronal pyroptosis.

Yayu Chen

Gen Wei

Xiaojin Feng

Enjun Lei

Lieliang Zhang

Dexmedetomidine enhances Mitophagy via PINK1 to alleviate hippocampal neuronal Pyroptosis and improve postoperative cognitive dysfunction in elderly rat.

右美托咪定通过PINK1增强线粒体自噬以减轻海马神经元焦亡并改善老年大鼠术后认知功能障碍。

The nucleus accumbens (NAc) is gaining interest as a target for deep brain stimulation (DBS) in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. In animal models, it has been shown that DBS of the NAc changes impulsive action. Here, we tested the hypothesis that a change in impulsive action by DBS of the NAc is associated with changes in dopamine levels. Rats received stimulating electrodes either in the NAc core or shell, and underwent behavioral testing in a reaction time task. In addition, in a second experiment, the effect of DBS of the NAc core and shell on extracellular dopamine and serotonin levels was assessed in the NAc and medial prefrontal cortex. Control subjects received sham surgery. We have found that DBS of the NAc shell stimulation induced more impulsive action but less perseverative checking. These effects were associated with increased levels of dopamine and serotonin in the NAc, but not in the medial prefrontal cortex. DBS of the NAc core had no effect on impulsive action, but decreased perseverative responses indicative of a better impulse control. In these subjects, no effects were found on neurotransmitter levels. Our data point out that DBS of the NAc shell has negative effects on impulsive action which is accompanied by increases of dopamine and serotonin levels in the NAc, whereas DBS of the NAc core has beneficial behavioral effects.

Thibaut Sesia

Vincent Bulthuis

Sonny Tan

Lee Wei Lim

Rinske Vlamings

Arjan Blokland

Harry W M Steinbusch

Trevor Sharp

Veerle Visser-Vandewalle

Yasin Temel

Deep brain stimulation of the nucleus accumbens shell increases impulsive behavior and tissue levels of dopamine and serotonin.

伏隔核壳深部脑刺激增加冲动行为及多巴胺和血清素组织水平。

The nucleus accumbens is gaining interest as a target for deep brain stimulation in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. Here, we tested the hypothesis that stimulation of the nucleus accumbens core and shell would have different effects on impulsivity. Rats received bilateral stimulation at the level of the nucleus accumbens core or shell during a reaction time task. Stimulation of the nucleus accumbens core significantly decreased impulsivity, while stimulation of the shell increased it. Our results support the hypothesis that the nucleus accumbens is a potential target to treat neuropsychiatric disorders related to impulsivity by deep brain stimulation. However, different behavioral effects resulting from stimulation of the subterritories should be taken into account.

Deep brain stimulation of the nucleus accumbens core and shell: opposite effects on impulsive action.

伏隔核核心与壳部深部脑刺激：对冲动行为的相反影响。

Cognitive dysfunction is the most severe non-motor symptom of Parkinson's disease (PD). Our previous study revealed that hydrogen sulfide (H2S) ameliorates cognitive dysfunction in PD, but the underlying mechanisms remain unclear. Hippocampal necroptosis plays a vital role in cognitive dysfunction, while the cGAS/STING pathway triggers necroptosis. To understand the mechanism underlying the inhibitory role of H2S in cognitive dysfunction of PD, we explored whether H2S reduces the enhancement of necroptosis and the activation of the cGAS/STING pathway in the hippocampus of the rotenone (ROT)-induced PD rat model.

Xin-Le Huang

Yu Hu

Wu Jiang

Jia-Mei Jiang

Wei Zou

Ping Zhang

Xiao-Qing Tang

Suppression of cGAS/STING pathway-triggered necroptosis in the hippocampus relates H2S to attenuate cognitive dysfunction of Parkinson's disease

海马cGAS/STING通路触发坏死性凋亡的抑制与H2S减轻帕金森病认知功能障碍相关

Charcot-Marie-Tooth type 1A (CMT1A) is the most common inherited peripheral dysmyelinating neuropathy. Although lower limb muscle weakness is the most important factor affecting the quality of life of patients with CMT1A, existing clinical measures for its evaluation have limitations, including low sensitivity in detecting disease progression. Electrical impedance myography (EIM) is a newer tool that enables noninvasive evaluation of muscle state by measuring muscle composition, and potentially supports the evaluation of neuromuscular disease progression and treatment effects. To determine the potential of EIM as a CMT1A biomarker, we obtained natural history data for EIM from the gastrocnemius muscle of the PMP22-C3 mice, an animal model of CMT1A. Alterations in the EIM parameters, weak hindlimb grip strength, decreased muscle fiber size, and changes in the mRNA expression of genes related to neuromuscular junction dysfunction were found. These changes were more pronounced at later stages (12 and 18 weeks of age) than at earlier stage (6 weeks of age), indicating that EIM can detect disease progression in PMP22-C3 mice. Our preclinical findings support the use of EIM as a potential translational biomarker for assessing progressive changes in the pathological muscle state in CMT1A.

Atsuki Taruta

Tetsuaki Hiyoshi

Akina Harada

Masato Nakashima

Electrical impedance myography detects progressive pathological alterations in the hindlimb muscle of the PMP22-C3 mice, an animal model of CMT1A

电阻抗肌图检测PMP22-C3小鼠后肢肌肉进行性病理改变，一种CMT1A动物模型

Due to the differences and variances in genetic background, in vitro and animal models cannot meet the modern medical exploration of real human brain structure and function. Recently, brain organoids generated by human pluripotent stem cells (hPSCs) can mimic the structure and physiological function of human brain, being widely used in medical research. Brain organoids generated from normal hPSCs or patient-derived induced pluripotent stem cells offer a more promising approach for the study of diverse human brain diseases. More importantly, the use of the established brain organoid model for drug evaluation is conducive to shorten the clinical transformation period. Herein, we summarize methods for the identification of brain organoids from cellular diversity, morphology and neuronal activity, brain disease modeling, toxicity testing, and drug evaluation. Based on this, it is hoped that this review will provide new insights into the pathogenesis of brain diseases and drug research and development, promoting the rapid development of brain science.

Na Xie

Jinrong Bai

Ya Hou

Jia Liu

Yi Zhang

Xianli Meng

Xiaobo Wang

hPSCs-derived brain organoids for disease modeling, toxicity testing and drug evaluation

人多能干细胞衍生的脑类器官用于疾病建模、毒性测试和药物评估

Clinical biomarkers are crucial for diagnosing and predicting outcomes in patients with traumatic brain injury (TBI). In this study, we performed an unbiased analysis of plasma proteins in acute TBI patients using bead-based multiplex assays and identified a strong positive correlation between LCN2 and IL-6 levels. Based on these findings, we hypothesized that LCN2 and IL-6 are closely related circulating biomarkers for TBI. Our previous and current studies demonstrate that the expression of LCN2, IL-6, and its receptors is upregulated in patients with chronic traumatic encephalopathy, in mouse models of traumatic and ischemic injury, and in an in vitro scratch injury model. Lcn2-deficiency reduced the injury-induced expression of IL-6 and its receptors in both animal and scratch injury models. These results suggest an augmented LCN2-dependent IL-6 signaling in the injured brain. As both LCN2 and IL-6 are secreted proinflammatory mediators, we further explored the possibility of cross-regulation between LCN2 and IL-6. In cultured glial cells, treatment with recombinant LCN2 protein enhanced the microglial expression of IL-6, while IL-6 protein treatment increased astrocytic LCN2 expression. Moreover, IL-6 expression and release were elevated in LCN2-overexpressing transgenic mice. Mechanistically, IL-6 enhanced astrocytic LCN2 expression through STAT3 signaling, while LCN2 upregulated microglial IL-6 expression through the NF-κB pathway. Taken together, our results suggest an important role of the LCN2-IL-6 axis in amplifying neuroinflammation through a positive feedback loop in secondary brain injury conditions. Finally, this study implies the utility of LCN2 and IL-6 as closely related biomarkers for TBI diagnosis and prognosis.

Jae-Hong Kim

Han-Gil Jeong

Seung Jae Hyeon

Uiyeol Park

Won-Jong Oh

Junmo Hwang

Hyun-Ho Lim

Pan-Woo Ko

Ho-Won Lee

Won-Ha Lee

Hoon Ryu

Kyoungho Suk

Crosstalk between lipocalin-2 and IL-6 in traumatic brain injury: Closely related biomarkers

创伤性脑损伤中脂质运载蛋白-2与白细胞介素-6的串扰：密切相关的生物标志物

Focal cortical infarction can result both in the accumulation of Aβ in as well as further secondary damage and inflammation within the ipsilateral thalamus. VX-765 is a potent and selective small-molecule capable of inhibiting caspase-1, which has been shown to exhibit active neuroprotection properties in multiple disease. However, the neuroprotection efficacy of VX-765 as a means of attenuating secondary damage after MCAO remains uncertain. As such, we sought to determine the ability of VX-765 to alter thalamic Aβ accumulation, secondary damage, and sensory deficits in rats of focal cortical infarction. A rat model of distal branch of middle cerebral artery occlusion (dMCAO) was used to evaluate the effects of the VX-765 on the secondary damage and β-amyloid accumulation in ipsilateral thalamus after dMCAO in rats. The activation of astrocyte and microglia, loss of neuron, and damage to sensory function were detected weekly till 4 weeks after modeling. VX-765 was injected intraperitoneally delayed after 7 days injury and the status of secondary damage, inflammation and β-amyloid accumulation in ipsilateral thalamus after dMCAO were examined.Our results revealed that VX-765 markedly reduce sensory deficits in these rats, suppressing secondary damage through reductions in APP and accumulations of Aβ with an accompanying reduction in both neuronal loss, astrocyte and microglia activation. VX-765 markedly inhibited NLRP3 and caspase-1, and downregulation of ASC, GSDMD, IL-1β, and IL-18 in the ipsilateral thalamus after MCAO. Our results further suggested that VX-765 may regulate secondary damage via control inflammation and suppressing the production of pro-inflammatory factors such as iNOS, TNF-α, IL-6 and COX2 that are produced downstream NF-κB signaling. Taken together, VX-765 is well-suited to attenuate secondary damage and accumulations of Aβ, improving recovery from sensory deficits and cognitive deficits after MCAO, at least in part via suppressing pyroptosis and inflammation.

Yu-Bin Liang

Ri-Xin Luo

Zhen Lu

Ying Mao

Ping-Ping Song

Qiao-Wei Li

Zhi-Qiang Peng

Yu-Sheng Zhang

VX-765 attenuates secondary damage and β-amyloid accumulation in ipsilateral thalamus after experimental stroke in rats.

VX-765 减轻大鼠实验性脑卒中后同侧丘脑的继发性损伤和β-淀粉样蛋白积聚

Abbreviation	Exp. Neurol.
Journal Impact	4.78
Quartiles(Global)	NEUROSCIENCES(Q1)

ISSN	0014-4886, 1090-2430
h-index	208

Publication Information	Publisher: Academic Press Inc.，Publishing cycle: Monthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1959，Proportion of original research papers: 86.06%，Self Citation Rate:4.30%， Gold OA Rate: 24.71%
Average review cycle	网友分享经验：平均1.0个月
Average recruitment ratio	网友分享经验：较易

Experimental Neurology

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