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。

Reciprocal communication between reactive astrocytes and microglial cells provides local, coordinated control over critical processes such as neuroinflammation, neuroprotection, and scar formation after CNS injury, but is poorly understood. The vasoactive peptide hormone endothelin (ET) is released and/or secreted by endothelial cells, microglial cells and astrocytes early after ischemic stroke and other forms of brain injury. To better understand glial cell communication after stroke, we sought to identify paracrine effectors produced and secreted downstream of astroglial endothelin receptor B (ETBR) signaling. Using a genetic loss-of-function screen, we identified angiopoietin-2 (Ang-2) as a factor produced by reactive astrocytes in response to ET. In experiments with primary adult astrocytes stimulated by IRL1620, a specific ETBR agonist, we found that ERK1/2 and NFkB mediated the effects of ET on Ang-2 production. To determine astroglial Ang-2 levels in vivo, reactive astrocytes expressing the high affinity glutamate transporter (GLAST, EAAT1) were isolated by magnetic-activated cell sorting 3 days after stroke. Astrocytes obtained from the ipsilateral hemisphere expressed significantly more Ang-2 compared with astrocytes isolated from the contralateral hemisphere, or from cortices of sham-operated (control) mice. Notably, analysis of microglia sorted from CX3CR1-eGFP mice demonstrated increased cell surface expression of Tie-2, the Ang-2 receptor, on cells obtained from ipsilateral versus contralateral tissue. Addition of recombinant Ang-2 to astrocyte-conditioned medium significantly increased the number of SIM-A9 murine microglial cells cultured under hypoxic conditions (1 % oxygen for 48 h). In transgenic GFAP-CreER™-EDNRB-fl/fl mice with stroke, conditional knockout of astroglial ETBR significantly decreased the number of proliferating cells in the peri-infarct area with a microglial phenotype (Ki67+/CD11b+). Our results indicate that Ang-2, and possibly other paracrine effectors functioning downstream of astroglial ETBR signaling, are important mediators of microglial cell dynamics after stroke.

John J McInnis

Matthew D LeComte

Leah F Reed

Emily E Torsney

Roxana Del Rio-Guerra

Matthew E Poynter

Jeffrey L Spees

Microglial cell proliferation is regulated, in part, by reactive astrocyte ETBR signaling after ischemic stroke.

缺血性卒中后反应性星形胶质细胞ETBR信号部分调控小胶质细胞增殖

Dendritic and axonal plasticity, which mediates neurobiological recovery after a stroke, critically depends on the mitochondrial function of neurons. To investigate, in vivo, neuronal mitochondrial function at the stroke recovery stage, we employed Mito-tag mice combined with cerebral cortical infection of AAV9 produced from plasmids carrying Cre-recombinase controlled by two neuronal promoters, synapsin-I (SYN1) and calmodulin-kinase IIa to induce expression of a hemagglutinin (HA)-tagged enhanced green fluorescence protein (EGFP) that localizes to mitochondrial outer membranes of SYN1 positive (SYN+) and CaMKIIa positive (CaMKIIa+) neurons. These mice were then subjected to permanent middle cerebral artery occlusion (MCAO) and sacrificed 14 days post stroke. Neuronal mitochondria were then selectively isolated from the fresh brain tissues excised from the ischemic core (IC), ischemic boundary zone (IBZ), as well as from the homologous contralateral hemisphere (CON) by anti-HA magnetic beads for functional analyses. We found that the bead pulled neuronal specific mitochondria were co-precipitated with GFP and enriched with mitochondrial markers, e.g. voltage-dependent anion channel, cytochrome C, and COX IV, but lacked the Golgi protein RCAS1 as well as endoplasmic reticulum markers: Heme‑oxygenase 1 and Calnexin, indicating that specific neuronal mitochondria have been selectively isolated. Western-blot data showed that oxidative phosphorylation (OXPHOS) components in SYN+ and CAMKII+ neuronal mitochondria were significantly decreased in the IBZ and further decreased in the IC compared to the contralateral tissue, which was associated with the significant reductions of mitochondrial function indicated by oxygen consumption rate (OCR) (p < 0.05, respectively, for both neuron types). These data suggest dysfunction of neuronal mitochondria post stroke is present during the stroke recovery stage. Collectively, for the first time, we demonstrated that using a Mito-tag mouse line combined with AAV9 carrying Cre recombinase approach, neuronal specific mitochondria can be efficiently isolated from the mouse brain to investigate their functional changes post stroke.

Yanfeng Li

Zheng Gang Zhang

Michael Chopp

Zhongwu Liu

William Golembieski

Julie Landschoot-Ward

Yi Zhang

Xian Shuang Liu

Hongqi Xin

Labeling and isolating cell specific neuronal mitochondria and their functional analysis in mice post stroke.

标记和分离细胞特异性神经元线粒体及其在卒中后小鼠中的功能分析

Despite advances in reperfusion therapies, ischemic stroke remains a major cause of long-term disability due to residual hypoxic lesions persisting after macrovascular reperfusion. These residual hypoxic lesions, caused by microvascular dysfunction, represent an important therapeutic target. We previously demonstrated that oxygen-glucose-deprived peripheral blood mononuclear cells (OGD-PBMCs) migrate to ischemic brain regions and promote functional recovery after stroke. This recovery occurs through mechanisms involving hypoxia-inducible factor-1α, exosomal miR-155-5p, and vascular endothelial growth factor (VEGF). However, it remains unclear whether OGD-PBMCs target hypoxic regions.

Takeshi Kanayama

Masahiro Hatakeyama

Natsuki Akiyama

Yutaka Otsu

Osamu Onodera

Takayoshi Shimohata

Masato Kanazawa

Oxygen-glucose-deprived peripheral blood mononuclear cells act on hypoxic lesions after ischemia-reperfusion injury.

缺氧缺糖的外周血单个核细胞对缺血再灌注损伤后缺氧病灶的作用

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

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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