Experimental Neurology最新文献

{"title":"KIF23 inhibition protects against perioperative neurocognitive disorders by hindering ROS/caspase-3/GSDME-mediated pyroptosis – Authors' reply","authors":"Shaoqun Tang, Xi Yu, Wei Wang, Zhongyuan Xia","doi":"10.1016/j.expneurol.2025.115445","DOIUrl":"10.1016/j.expneurol.2025.115445","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115445"},"PeriodicalIF":4.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: “KIF23 inhibition protects against perioperative neurocognitive disorders by hindering ROS/caspase-3/GSDME-mediated pyroptosis” by Tang et al.","authors":"Parth Aphale, Himanshu Shekhar, Shashank Dokania","doi":"10.1016/j.expneurol.2025.115446","DOIUrl":"10.1016/j.expneurol.2025.115446","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115446"},"PeriodicalIF":4.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Farrerol confers neuroprotection in spinal cord injury by regulating macrophages/microglia polarization through the JAK2/STAT3 pathway","authors":"Yue Chen ,&nbsp;Lü Ren ,&nbsp;Jinzhi Xia ,&nbsp;Bohan Li ,&nbsp;Yi Yang ,&nbsp;Jing Li ,&nbsp;Lu Tao ,&nbsp;Xue Song ,&nbsp;Hezuo Lü ,&nbsp;Jianguo Hu","doi":"10.1016/j.expneurol.2025.115448","DOIUrl":"10.1016/j.expneurol.2025.115448","url":null,"abstract":"<div><h3>Background and aims</h3><div>Spinal cord injury (SCI) causes secondary damage characterized by neuroinflammation and imbalanced macrophages/microglia polarization, worsening neuronal loss and functional decline. Farrerol (FAR), a natural flavonoid with anti-inflammatory properties, has not been studied for SCI treatment. This work assesses FAR's neuroprotection through macrophages/microglia polarization regulation and explores its mechanisms.</div></div><div><h3>Methods</h3><div>C57BL/6 mice with spinal cord injury were randomly assigned to three groups: Sham, SCI, and SCI + FAR. Motor function was evaluated using locomotor scoring, while lesion size, myelin integrity, and neuronal apoptosis were assessed via histology, immunofluorescence, and Western blot. Spinal inflammatory cytokine, macrophages/microglia activation, and polarization were analyzed by qRT-PCR, ELISA, immunofluorescence, and flow cytometry. LPS-stimulated BV2 microglia and BV2-HT22 co-cultures evaluated FAR's effects on cytokine secretion, macrophages/microglia phenotypes, and neuronal survival. Signaling mechanisms were further examined via Western blot and immunofluorescence.</div></div><div><h3>Results</h3><div>FAR treatment significantly enhanced motor recovery in SCI mice, evidenced by elevated Basso Mouse Scale (BMS) scores, increased inclined plane angles, improved swimming performance, and refined gait patterns. It reduced lesion area, preserved myelin integrity, and attenuated neuronal apoptosis. FAR downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), suppressed macrophages/microglia hyperactivation while upregulating IL-10, and shifted M1/M2 polarization toward neuroprotective M2 phenotypes. In LPS-stimulated BV2 microglia, FAR attenuated inflammatory responses, inhibited M1 markers, enhanced M2 markers, and rescued HT22 neuronal apoptosis in co-cultures. These therapeutic effects may be mediated through suppression of JAK2/STAT3 phosphorylation.</div></div><div><h3>Conclusions</h3><div>FAR promotes functional recovery after spinal cord injury by modulating macrophages/microglia M1/M2 polarization through JAK2/STAT3 pathway inhibition, thereby attenuating neuroinflammation and neuronal death. These findings provide novel evidence supporting targeted immunomodulation for SCI treatment.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115448"},"PeriodicalIF":4.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term intermittent theta burst stimulation alleviates Parkinson's disease-related cognitive impairment by modulating GluN2B in the dorsal hippocampus","authors":"Xiang Wu ,&nbsp;Yanping Hui ,&nbsp;Ling Wang ,&nbsp;Hongfei Qiao ,&nbsp;Yixuan Wang ,&nbsp;Yihua Bai ,&nbsp;Qingfeng Sun ,&nbsp;Shasha Gao ,&nbsp;Qiaojun Zhang ,&nbsp;Libo Li","doi":"10.1016/j.expneurol.2025.115439","DOIUrl":"10.1016/j.expneurol.2025.115439","url":null,"abstract":"<div><div>Cognitive impairment is one of the typical non-motor symptoms of Parkinson's disease (PD) that severely affects the quality of life of patients. However, limited treatments are currently available, suggesting the urgent need for new therapeutic approaches. Intermittent theta burst stimulation (iTBS), an updated pattern of high-frequency repetitive transcranial magnetic stimulation, can potentially improve cognitive function. However, its efficacy on PD-related cognitive impairment and the mechanism underlying it remain unclear. In this study, we found that unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) impaired hippocampus-dependent memory, decreased the expression of GluN2B at both the total and membrane protein levels, reduced the concentration of intracellular Ca²⁺, and resulted in hyperactive theta power in the dorsal hippocampus (dHip) in rats. Fourteen days of iTBS treatment improved the impaired hippocampus-dependent memory in the lesioned rats, which could last for at least 10 days. In addition, iTBS treatment up-regulated the expression of GluN2B at total and membrane protein levels, elevated intracellular Ca²⁺ concentration, and normalized the aberrantly high theta power in the dHip. Furthermore, iTBS treatment failed to improve hippocampus-dependent memory and normalize the aberrant theta power after knocking down the hippocampal GluN2B. Collectively, these findings suggest that 14-day iTBS treatment alleviates hippocampus-dependent memory impairment in PD, which is achieved by up-regulating the expression of the GluN2B, followed by increasing the level of intracellular Ca²⁺ concentration and normalizing hyperactive theta rhythm in the dHip.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115439"},"PeriodicalIF":4.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Pyridoxal Phosphate inhibits alpha-synuclein-induced ferroptosis by activating GOT1 to enhance the methionine salvage pathway in Parkinson's Disease” [Experimental Neurology (2025) 115411]","authors":"Xudong Min ,&nbsp;Zhuolin Du ,&nbsp;Jirui Wei ,&nbsp;Zhao Yuan ,&nbsp;Yang She ,&nbsp;Xiayu Jin ,&nbsp;Zequn Su ,&nbsp;Hengxu Mao ,&nbsp;Jing Cai ,&nbsp;Zhiyuan Zhu ,&nbsp;Xiaozheng He","doi":"10.1016/j.expneurol.2025.115429","DOIUrl":"10.1016/j.expneurol.2025.115429","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115429"},"PeriodicalIF":4.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypocretin/orexin peptide release occurs mostly extrasynaptically, is self-controlled, and specifically enhanced in female rats","authors":"Carlos Carrera-Cañas,&nbsp;Isabel de Andrés,&nbsp;Marta Callejo,&nbsp;Miguel Garzón","doi":"10.1016/j.expneurol.2025.115438","DOIUrl":"10.1016/j.expneurol.2025.115438","url":null,"abstract":"<div><div>The hypothalamic hypocretinergic/orexinergic (Hcrt/Ox) system comprises two neuropeptides -Hcrt1/OxA and Hcrt2/OxB- and two receptors -Hcrt/OxR1 and Hcrt/OxR2- which perform multiple modulatory actions. Its neurotransmission mechanism remains poorly understood despite its malfunction entails narcolepsy and low cerebrospinal fluid (CSF)-Hcrt1/OxA levels is the most specific biomarker of the disease. This work examines: (1) synaptic and volume Hcrt/Ox transmission types; (2) Hcrt/Ox receptors involvement in Hcrt/Ox-peptide release/synthesis; and (3) Hcrt/Ox system sexual dimorphism.</div><div>Axonal central/peripheral distribution of dense-core vesicles (dcv) containing Hcrt1/OxA and small synaptic vesicles (ssv) loaded with glutamate was analyzed by electron microscopy in naïve rats immunolabeled for Hcrt1/OxA at the locus coeruleus area. In addition, two sets of mixed male and female rats receiving intraperitoneal (i.p.) injections of either DMSO (vehicle) or 30 mg/kg suvorexant (a dual Hcrt/Ox receptor antagonist) for 7 days were used. Hcrt1/OxA was measured in CSF and in synaptic terminals (synaptosome preparations) from the oral pontine tegmentum (OPT) of these rats using ELISA.</div><div>Hcrt1/OxA-loaded dcv were more clustered in the axonal periphery than ssv, and Hcrt1/OxA enrichment was higher in CSF than in OPT-synaptosome preparations. Hcrt/Ox transmission blockade with suvorexant produced intracellular accumulation of Hcrt1/OxA, in parallel to its previously reported decrease in CSF. Female rats showed higher Hcrt1/OxA basal levels than males in CSF but not in OPT-Syn samples.</div><div>Our results support the notion that: (1) volume/extrasynaptic Hcrt/Ox-peptide release is greater than synaptic/perisynaptic release, (2) Hcrt/OxR1 controls Hcrt/Ox-peptide release rather than synthesis in Hcrt/Ox neurons, and (3) Hcrt/Ox volume neurotransmission is enhanced in females.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115438"},"PeriodicalIF":4.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-155-5p and miR-674-3p presence in peripheral blood and white blood cells as potential early biomarkers of temporal lobe epilepsy","authors":"Kinga Szydlowska ,&nbsp;Piotr Chroscicki ,&nbsp;Maciej Olszewski ,&nbsp;Karolina Nizinska ,&nbsp;Aleksandra Stepniak ,&nbsp;Katarzyna Piwocka ,&nbsp;Katarzyna Lukasiuk","doi":"10.1016/j.expneurol.2025.115430","DOIUrl":"10.1016/j.expneurol.2025.115430","url":null,"abstract":"<div><div>Epilepsy frequently develops as a result of a brain insult, for example, brain injury or stroke. Currently, no tools are allowing us to predict which trauma patients will eventually develop epilepsy. There is evidence that microRNA levels are altered in the blood, making them attractive candidates for peripheral biomarkers of epilepsy. We analyzed whole blood miRNA levels using a dual-platform approach and selected miR-155-5p and miR-674-3p as candidates for biomarkers of early changes in asymptomatic temporal lobe epilepsy. Additionally, we assessed white blood cell subpopulations containing miR-155-5p and miR-674-3p in control and stimulated animals, as well as in control and symptomatic or asymptomatic animals in the amygdala stimulation model. The first proposed putative early biomarker of epilepsy is the relative proportion of CD45RA⁺ B cells containing miR-155-5p and/or miR-674-3p. Others are an increased number of CD45RA⁺ B cells containing either miR-155-5p or both miR-155-5p and miR-674-3p, or a decreased number of CD161+ NK cells that do not contain either miR-155-5p or miR-674-3p. Additionally, we found that the decreased number of CD4⁺ T cells can. These putative biomarkers should be subjected to further studies in other epilepsy models and larger cohorts.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115430"},"PeriodicalIF":4.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep deprivation-induced cognitive impairment: Unraveling the role of neuroinflammation","authors":"Xiao-Lei Yuan,&nbsp;Chun-Yan Wang","doi":"10.1016/j.expneurol.2025.115419","DOIUrl":"10.1016/j.expneurol.2025.115419","url":null,"abstract":"<div><div>Sleep deprivation (SD) is a common public health issue linked to cognitive decline and neurodegenerative diseases. SD-induced cognitive impairment is closely linked to neuroinflammation, yet the underlying mechanisms remain incompletely understood. This review highlights neuroinflammation as a key mechanism linking SD to cognitive impairment, focusing on microglial activation via the NF-κB pathway, astrocyte dysfunction, oxidative stress, and gut-brain axis disruption. Chronic SD triggers pro-inflammatory cytokine release, neurotransmitter imbalance, and impaired synaptic plasticity, leading to neuronal damage. It also disrupts glymphatic clearance, promoting neurotoxic metabolite buildup. Notably, neuroinflammation and neurotransmitter imbalance reinforce each other in a vicious cycle that accelerates cognitive deterioration. Finally, we outline therapeutic strategies targeting neuroinflammation, including pharmacological agents, natural compounds, and microbiota modulation, that may help preserve cognitive function.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115419"},"PeriodicalIF":4.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemogenetic activation of VTA neurons induces anxiety-like behavior in a Parkinson's disease model","authors":"Xiaying Lu ,&nbsp;Yue Qi ,&nbsp;Jinhua Xue ,&nbsp;Xiaolu Tang","doi":"10.1016/j.expneurol.2025.115425","DOIUrl":"10.1016/j.expneurol.2025.115425","url":null,"abstract":"<div><div>As Parkinson's disease (PD) advances, there may be a compensatory activation of neurons in the ventral midbrain, potentially linked to the manifestation of non-motor symptoms in individuals with PD. These non-motor symptoms, such as anxiety, often precede the onset of motor symptoms, with female patients generally exhibiting higher levels of anxiety. Nonetheless, the precise mechanisms underlying this phenomenon remain inadequately elucidated. The ventral tegmental area (VTA) of the midbrain functions as a pivotal nucleus capable of encoding both positive and negative emotional signals, potentially contributing to the development of anxiety comorbidities in patients with PD. In this study, we utilized a combination of chemogenetics, behavioral assessments, and morphological analyses to demonstrate that the heightened activity of VTA neuron populations, especially dopaminergic neurons induces sex-specific anxiety-related behaviors in mice. This phenomenon may be associated with the activation of the VTA-NAC and VTA-vHPC neural circuits. Our findings highlight the critical role of VTA neuron populations, especially dopaminergic neurons in early PD-related anxiety. They offer a valuable experimental framework for elucidating the neural mechanisms underlying anxiety in PD, thereby establishing a foundation for the development of early intervention strategies.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"393 ","pages":"Article 115425"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kapβ2 attenuates post-anesthetic neurocognitive dysfunction by resolving HnRNPA2/B1 fibrillary tangles in a rat model of mild cognitive impairment","authors":"Miao Zhang ,&nbsp;Xinyi Wang ,&nbsp;Chenyi Yang ,&nbsp;Zixuan Wang ,&nbsp;Huihui Liao ,&nbsp;Lin Zhang ,&nbsp;Xi Xin ,&nbsp;Haiyun Wang","doi":"10.1016/j.expneurol.2025.115426","DOIUrl":"10.1016/j.expneurol.2025.115426","url":null,"abstract":"<div><h3>Background</h3><div>Patients with mild cognitive impairment (MCI) before surgery have a higher incidence of perioperative neurocognitive disorders (PND) and a higher rate of progression to dementia than those without MCI; however, the underlying mechanisms are unclear. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is an RNA-binding protein (RBP) that forms fibrillary tangles via a steric zipper motif. Abnormal accumulation of HnRNPA2/B1 is strongly correlated with local neurodegeneration and cognitive impairment. However, karyopherin-β2 (Kapβ2), a nuclear import receptor, can specifically recognize hnRNPA2/B1 and alleviate the neurotoxicity caused by its accumulation in the cytoplasm.</div></div><div><h3>Methods</h3><div>In this study, to explore the role of hnRNPA2/B1 in PND and whether overexpression of Kapβ2 reduces hnRNPA2/B1 fibrillary tangle formation, we compared different anesthetics (3 % sevoflurane, 40 mg/kg/h propofol, and 9 % desflurane) to the incidence of PND, the integrity of hippocampal microstructure, as well as the distribution and function of hnRNPA2/B1 in a rat model of MCI after open reduction and internal fixation (ORIF) of tibial fractures by using Morris water maze (MWM), brain magnetic resonance diffusion tensor imaging (DTI), immunofluorescence staining, RT-qPCR, and western blot. Simultaneously, to assess the effect of Kapβ2 on cognitive function after sevoflurane+surgery, the most severe model for PND, Kapβ2 overexpressing adeno-associated virus was stereotactically injected in the hippocampus of rats.</div></div><div><h3>Results</h3><div>Sevoflurane induced severe hnRNPA2/B1 fibrillary tangles and cognitive decline. Kapβ2 overexpression reduced cytoplasmic hnRNPA2/B1 accumulation and attenuated cognitive impairment.</div></div><div><h3>Conclusions</h3><div>This study revealed the pathological mechanism of hnRNPA2/B1 cytoplasmic fibrillary tangle induced by anesthesia used in surgery to promote the occurrence of PND in MCI rats and restored the nuclear localization of hnRNPA2/B1 and neuronal function through the overexpression of Kapβ2, which provides a new idea for perioperative neuroprotection and rehabilitation in patients with MCI who have a high risk of conversion to dementia.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"394 ","pages":"Article 115426"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}