Neuroscience最新文献

{"title":"DJ-1/PARK7 in Parkinson’s disease: mechanisms of pathogenesis and therapeutic potential","authors":"Weicong Bao ,&nbsp;Ying Ge ,&nbsp;Juan Huang ,&nbsp;Yuanyuan Li ,&nbsp;Yong Luo ,&nbsp;Nanqu Huang","doi":"10.1016/j.neuroscience.2025.09.025","DOIUrl":"10.1016/j.neuroscience.2025.09.025","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, characterized by the substantial degeneration of nigral dopaminergic neurons, the accumulation of alpha-synuclein, and the intraneuronal formation of Lewy bodies. DJ-1 is a multifaceted protein that has been linked to the pathogenesis of neurodegenerative diseases. Recent research has highlighted a potential role for DJ-1 in PD. This protein plays a critical role in maintaining mitochondrial homeostasis, modulating apoptosis, facilitating chaperone-mediated autophagy (CMA), and stabilizing dopamine levels by interacting with various signaling pathways, transcription factors, and molecular chaperones. The potential of DJ-1 as a therapeutic target for PD is apparent. In this review, we delineate the specific contributions of DJ-1 to the pathogenesis of PD. Furthermore, we discuss the therapeutic developments centered on DJ-1 in the context of neurodegeneration associated with PD.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"587 ","pages":"Pages 1-13"},"PeriodicalIF":2.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regrouping reverses social impairments and prefrontal parvalbumin-perineuronal nets alterations induced by post-weaning social isolation in male mice","authors":"Siddharth Varman,&nbsp;Grace Caldwell,&nbsp;Laurence Coutellier","doi":"10.1016/j.neuroscience.2025.09.030","DOIUrl":"10.1016/j.neuroscience.2025.09.030","url":null,"abstract":"<div><div>Social isolation during early development can lead to abnormal adult behavior. These behavioral deficits are often associated with disruptions of perineuronal nets (PNNs), a condensed form of the brain’s extracellular matrix. PNNs regulate neuroplasticity by enwrapping parvalbumin-expressing (PV) interneurons, and abnormal maturation of PNN in early life has been associated with behavioral deficits reminiscent of those following isolation. Past studies demonstrate that social regrouping following early isolation can improve behavioral deficits, but the underlying mechanisms of this recovery are unknown. This study aims to establish the effects of regrouping on PNNs as a potential cellular mediator of the behavioral rescue. We hypothesize that regrouping mice during adolescence will rescue early isolation-induced behavioral deficits associated with PNN restoration. We assigned male mice to group-housed, isolated, or isolated/regrouped conditions from weaning age until end of adolescence (postnatal day 21 to 67; N = 8–10/group). Behaviors were assessed in the open field, novel object recognition, Y-maze, and social interaction tests. Number of PV cells and PNNs were quantified in the prefrontal cortex (PFC), dorsal and ventral hippocampus. Our results showed that early isolation led to hypersociability, which was rescued by regrouping; however regrouping also increased anxiety. Furthermore, isolation reduced the propotion of PV cells surrounded by PNNs in the PFC, and regrouping reversed this effect and increased the total PNN count in PFC while it decreased PV/PNN count in the ventral hippocampus. These findings suggest that behavioral improvements in the social domain may be associated with region-specific changes in PV interneuron plasticity.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"586 ","pages":"Pages 77-87"},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micron-scale wireless electrical stimulation suppresses seizure-Like activity via GABAergic modulation in hippocampal slices","authors":"Lei Dong ,&nbsp;Meng-Ying Luan ,&nbsp;Wan-Ying Xing ,&nbsp;Ye-Nan Qi ,&nbsp;Chun-Xiao Tian ,&nbsp;Yu Zheng","doi":"10.1016/j.neuroscience.2025.09.031","DOIUrl":"10.1016/j.neuroscience.2025.09.031","url":null,"abstract":"<div><div>Temporal lobe epilepsy (TLE) is a chronic neurological disorder characterized by abnormal neuronal discharges, often presenting as recurrent seizures, impaired consciousness, and other neurological impairments. Traditional wireless neuromodulation methods are constrained by limited spatial resolution and diffuse electromagnetic coverage, restricting their precision in targeting epileptogenic zones. In this study, we developed a micron-scale wireless electrical stimulation (ES) device based on magnetic inductive coupling to address these limitations and enable focal neuromodulation. For the first time, temporally patterned ES protocols were applied to hippocampal brain slices from juvenile rats exhibiting chemically induced epileptiform activity. To probe the underlying mechanism, the GABA receptor antagonist Bicuculline (BIC) was administered. The results revealed that ES significantly reduced the amplitude, duration, and frequency of epileptiform discharges. Upon BIC application, these suppressive effects were notably reversed, suggesting that the therapeutic action of ES is mediated, at least in part, through GABAergic pathways. This work provides novel insight into the mechanistic basis and therapeutic potential of micron-scale wireless stimulation for epilepsy intervention, and lays a foundation for its future clinical translation in neuromodulation strategies.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"586 ","pages":"Pages 32-43"},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating artificial intelligence with small molecule therapeutics and precision medicine for neurochemical understanding of Alzheimer’s diseases","authors":"Zafer Saad Alshehri","doi":"10.1016/j.neuroscience.2025.08.055","DOIUrl":"10.1016/j.neuroscience.2025.08.055","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is the most common neurodegenerative condition and continues to pose significant clinical and research challenges due to its complex causes and limited treatment success. Conventional therapies have primarily focused on amyloid-beta (Aβ) and tau proteins, but these efforts have yet to produce optimal results. This review explores emerging interdisciplinary strategies that integrate artificial intelligence (AI), small molecule drugs, and precision treatments to tackle AD’s intricacies. AI has significantly enhanced early detection, neuroimaging, and biomarker discovery using machine learning and deep learning. These state-of-art methods helps to analyze biomarker profiles and imaging data, thereby enabling tailored diagnostic and therapeutic strategies for individual patients. At the same time, computational methods have expedited the development of small molecules targeting Aβ buildup, tau pathology, and inflammation. Emerging treatments, including monoclonal antibodies, RNA-based therapies, and nanotechnology, provide promising alternatives to conventional approaches. The integration of AI with multi-omics and structure-guided drug design supports the creation of precise, individualized treatments. However, challenges in ethics, regulation, and clinical application persist. This review emphasizes the collaborative potential of AI, pharmacology, and biomedical engineering in revolutionizing AD treatment, highlighting the need for cross-disciplinary efforts to confront this urgent neurological condition.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"586 ","pages":"Pages 44-57"},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-filter stacking in inception V3 for enhanced Alzheimer’s severity classification","authors":"Ateeqa Iqbal ,&nbsp;Khalid Iqbal ,&nbsp;Yaser Ali Shah ,&nbsp;Farman Ullah ,&nbsp;Jebran Khan ,&nbsp;Shumayla Yaqoob","doi":"10.1016/j.neuroscience.2025.08.049","DOIUrl":"10.1016/j.neuroscience.2025.08.049","url":null,"abstract":"<div><div>Alzheimer’s disease, a progressive neurodegenerative disorder, is characterized by a decline in brain volume and neuronal loss, with early symptoms often presenting as short-term memory impairment. Automated classification of Alzheimer’s disease remains a significant challenge due to inter-patient variability in brain morphology, aging effects, and overlapping anatomical features across different stages. While traditional machine learning techniques, such as Support Vector Machines (SVMs) and various Deep Neural Network (DNN) models, have been explored, the need for more accurate and efficient classification techniques persists. In this study, we propose a novel approach that integrates Multi-Filter Stacking with the Inception V3 architecture, referred to as CASFI (Classifying Alzheimer’s Severity using Filter Integration). This method leverages diverse convolutional filter sizes to capture multiscale spatial features, enhancing the model’s ability to detect subtle structural variations associated with different Alzheimer’s disease stages. Applied to MRI data, CASFI achieved an accuracy of 97.27%, outperforming baseline deep learning models and traditional classifiers in both accuracy and robustness. This approach supports early diagnosis and informed clinical decision-making, providing a valuable tool to assist healthcare professionals in managing and planning treatment for Alzheimer’s patients.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"586 ","pages":"Pages 21-31"},"PeriodicalIF":2.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An evidence-based analysis of machine learning prediction models for cognitive impairment in cerebral small vessel disease","authors":"Qi Wu ,&nbsp;Jupeng Zhang ,&nbsp;Peng Lei ,&nbsp;Zhihao Zhang ,&nbsp;Xiqi Zhu ,&nbsp;Changhui Huang","doi":"10.1016/j.neuroscience.2025.09.021","DOIUrl":"10.1016/j.neuroscience.2025.09.021","url":null,"abstract":"<div><div>Early identification of cerebral small vessel disease (CSVD) patients with a higher risk of developing cognitive impairment is essential for timely intervention and improved patient outcomes. Machine learning (ML) has emerged as a promising technique for cognitive impairment in CSVD. This study aims to conduct a thorough <em>meta</em>-analysis and comparison of published ML prediction models for cognitive impairment in patients with CSVD. Relevant studies were retrieved from four databases: PubMed, Embase, Web of Science, and the Cochrane Library. A <em>meta</em>-analysis of the C-index was performed using a random-effects model, while a bivariate mixed-effects model was used to calculate the pooled sensitivity and specificity. In addition, to limit the influence of heterogeneity, we also performed sensitivity analyses, a <em>meta</em>-regression, and subgroup analysis. Included for analysis were 13 studies involving 3444 patients. The pooled C-index, sensitivity, and specificity were 0.84 (95% CI 0.79–0.90), 0.83 (95% CI 0.78–0.88), and 0.80 (95% CI 0.71–0.86), respectively. As one of the most commonly used ML methods, logistic regression achieved a total merged C-index of 0.81, while non logistic regression models performed better with a total merged C-index of 0.86. Our findings indicate that ML models holds significant promise in forecasting the risk of cognitive impairment in patients with CSVD. However, future high-quality research that externally validates the algorithm through prospective studies with larger, more diverse cohorts is needed.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"586 ","pages":"Pages 100-109"},"PeriodicalIF":2.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental SHQ1 variants navigate the control of apoptosis, endoplasmic reticulum stress, and oxidative stress in neuroblastoma cells","authors":"Huei-Jane Lee ,&nbsp;Chi-Ren Tsai ,&nbsp;Ching-Shiang Chi ,&nbsp;Hsin-Wen Liang ,&nbsp;Hsiu-Fen Lee","doi":"10.1016/j.neuroscience.2025.09.017","DOIUrl":"10.1016/j.neuroscience.2025.09.017","url":null,"abstract":"<div><div>SHQ1 binding to dyskerin/NAP57 is crucial for the assembly of H/ACA small nucleolar ribonucleoproteins (snoRNPs), which play essential roles in ribosome biogenesis and spliceosome function. Additionally, SHQ1 has been implicated in tumor suppression by interacting with the endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 (GRP78), thereby promoting apoptosis. Recent studies have identified biallelic <em>SHQ1</em> causative variants in patients with neurodevelopment disorders, however, their impact on the tumor remains unclear. To investigate the role of neurodevelopment-associated SHQ1 variants in tumor cells, wild-type or three <em>SHQ1</em> variants (<em>SHQ1</em>-Y65X, <em>SHQ1</em>-V271E, or <em>SHQ1</em>-L333V) were transfected into human SH-SY5Y neuroblastoma cells. Wild-type SHQ1 was found to enhance caspase-3 cleavage and increase terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) signals, accompanied by an upregulation of ER stress-related proteins, ultimately leading to apoptosis. In contrast, all three <em>SHQ1</em> variants exhibited reduced apoptosis and lower expression of ER stress-related proteins. Despite these functional differences, the binding affinity between SHQ1 and GRP78 remained unchanged across all variants. Furthermore, wild-type <em>SHQ1</em> induced an increase in reactive oxygen species (ROS) levels in SH-SY5Y cells, whereas the <em>SHQ1</em> variants were associated with decreased ROS production. These findings suggest that three neurodevelopment-associated <em>SHQ1</em> variants attenuate ROS generation, apoptotic signaling, and ER stress while maintaining their interaction with GRP78. In conclusion, this study demonstrates that SHQ1 modulates neuroblastoma cell apoptosis through the regulation of ER stress, ROS production, and apoptotic pathways. The attenuated apoptotic response observed in <em>SHQ1</em> variants provides insight into their potential role in neuroblastoma pathophysiology.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"586 ","pages":"Pages 1-8"},"PeriodicalIF":2.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased seizure susceptibility and neocortical excitability in TcMAC21 Down syndrome mice","authors":"Viveka Chinnasamy,&nbsp;Carl E. Stafstrom,&nbsp;Li-Rong Shao","doi":"10.1016/j.neuroscience.2025.09.016","DOIUrl":"10.1016/j.neuroscience.2025.09.016","url":null,"abstract":"<div><div>Seizures are a common comorbidity in children with Down syndrome (DS) yet seizure genesis in the DS brain is poorly understood. The two most common types of seizures in DS patients are infantile spasms (IS) and generalized tonic-clonic seizures. Using a novel humanized DS model (TcMAC21), we revealed an increased propensity to IS associated with a heightened neocortical excitation-inhibition ratio. Here, we examined the susceptibility of TcMAC21 mice to flurothyl-induced tonic-clonic type seizures and their propensity to epileptiform activity in neocortical-hippocampal slices. At postnatal day (P) 9–11, TcMAC21 mice exhibited significantly shorter latencies to flurothyl seizures but similar seizure durations compared with euploid controls. At P17-18, TcMAC21 mice showed both shorter seizure latencies and longer seizure durations than euploid mice. In neocortical-hippocampal slices, the frequency and duration of spontaneous epileptiform bursts (induced by 0 Mg²⁺ and 4-aminopyridine) in hippocampal CA3 and neocortical layers II/III and V were not significantly different between the euploid and TcMAC21 mice. In addition, we assessed evoked responses in layer II/III by electrical stimulation at the junction of layer VI and white matter, in the presence of a GABA_A receptor blocker, gabazine (1 uM). At P9-P13, evoked responses in layer II/III were similar between TcMAC21 and euploid mice; however, at P17-P20, the responses were significantly greater in TcMAC21 than euploid controls. Together, these data show that TcMAC21 mice exhibit heightened susceptibility to tonic-clonic seizures and an age-dependent increased neocortical excitability compared to euploid mice. These results provide new insights into the pathophysiology of seizures in DS.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 408-417"},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered motor activity and social behavior in zebrafish lacking the Hcn2b ion channel","authors":"Roberto Rodríguez-Ortiz ,&nbsp;Juan Pablo Fernández-Rosales,&nbsp;María Fernanda García-Peña,&nbsp;Adan Hernández,&nbsp;A. Edith Espino-Saldaña,&nbsp;Ataúlfo Martínez-Torres","doi":"10.1016/j.neuroscience.2025.09.020","DOIUrl":"10.1016/j.neuroscience.2025.09.020","url":null,"abstract":"<div><div>HCN channels are widely expressed in the brain and heart where they contribute to a variety of functions, including pacemakers, control of rhythmic firing, regulation of neuronal excitability and synaptic plasticity. Here, using zebrafish <em>Danio rerio</em>, we describe the brain and heart expression of <em>hcn2b</em> mRNA, the orthologous gene of human <em>HCN2</em>, and show that a loss of function of the <em>hcn2b</em> gene is associated with a slight, though not statistically significant, increase in basal electrical brain activity and <em>fosab</em> expression. We demonstrate that <em>hcn2b</em> mutants increase motor activity during the day-cycle and show social aversion. Our findings provide evidence that lack of Hcn2b channel function affects social behavior, supporting its relevance as a zebrafish model for studying HCN2-related neurological disorders.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"586 ","pages":"Pages 58-65"},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural instability in the left middle temporal gyrus associated with second language reading difficulties in Chinese children","authors":"Jia Zhang ,&nbsp;Hehui Li ,&nbsp;Manli Zhang ,&nbsp;Jie Chen ,&nbsp;Xiujie Yang ,&nbsp;Xiaoxia Feng ,&nbsp;Guosheng Ding ,&nbsp;Xiangzhi Meng","doi":"10.1016/j.neuroscience.2025.09.019","DOIUrl":"10.1016/j.neuroscience.2025.09.019","url":null,"abstract":"<div><div>Several neuroimaging studies have examined the neural basis of reading impairment, which were primarily based on univariate activation analysis. However, it remains unclear whether and which aspect of the neural representations are different in children with reading impairment. Using functional magnetic resonance imaging, we investigated this issue in Chinese-English bilingual children with diverse reading abilities. The neural representation was differentiated into representational stability and distinctiveness. The results showed that the difference of representational stability in the left middle temporal gyrus was specific to children with second language reading impairment. Moreover, the representational stability in the left middle temporal gyrus was indeed associated with second language reading ability. In addition, children with second language reading impairment also demonstrated differences of representational distinctiveness in the right inferior temporal gyrus. Our findings contribute to a better understanding of the universal and specific mechanisms of reading impairment at different aspects of the neural representation.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"586 ","pages":"Pages 9-20"},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}