Neuroscience最新文献

{"title":"Advancing nanotheranostics for neuro-immunological disorders: current status and future prospects","authors":"Sakshi Rai ,&nbsp;Amritha Nair ,&nbsp;Zirha Saleem ,&nbsp;Suman Kumar Ray ,&nbsp;Jagat R. Kanwar ,&nbsp;Sukhes Mukherjee","doi":"10.1016/j.neuroscience.2025.08.051","DOIUrl":"10.1016/j.neuroscience.2025.08.051","url":null,"abstract":"<div><div>Neuroimmunological disorders involve complex interactions between the nervous and immune systems, leading to various severe neurological conditions such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. These disorders are characterized by immune-mediated damage or inflammation within nervous tissue, resulting in cognitive deficits, movement issues, sensory impairments, and other neurological problems. They can affect people of all ages, but incidence increases significantly with advancing age, making them a growing public health concern. As the global population ages, the prevalence of neuroimmunological diseases is expected to rise sharply. Projections indicate that by 2050, approximately 150 million individuals worldwide may suffer from dementia-related disorders alone, with an economic burden reaching around $10 trillion. Current therapies mainly focus on symptom management, aiming to slow disease progression and improve quality of life. Emerging therapeutic strategies show promise, particularly nanomedicine, which employs nanoscale materials to deliver drugs precisely to affected tissues. This targeted approach reduces side effects and increases treatment effectiveness. Additionally, natural products and plant-based compounds are gaining attention for their neuroprotective effects, as they can modulate pathways involved in neuronal survival, repair, and immune regulation. Future research aims to deepen understanding of the molecular and genetic mechanisms underlying these disorders through advanced experimental models and technologies. These insights will facilitate the development of innovative therapies targeting neuroinflammation and immune dysregulation, with the goal of preventing disease progression or even achieving cures. Continued progress in neuroimmunology offers hope for improved treatment outcomes, reduced disease burden, and transformative advances in neurological healthcare worldwide.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 233-248"},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001000","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":"A single-center retrospective study on clinical features and outcomes of perimesencephalic non-aneurysmal subarachnoid hemorrhage patients","authors":"Chenchen Wang ,&nbsp;Xu Wang ,&nbsp;Yang Gao ,&nbsp;Yuwei Han,&nbsp;Da Huo,&nbsp;Xiaoming Li,&nbsp;Guobiao Liang","doi":"10.1016/j.neuroscience.2025.08.064","DOIUrl":"10.1016/j.neuroscience.2025.08.064","url":null,"abstract":"<div><div>Perimesencephalic non-aneurysmal subarachnoid hemorrhage (pmSAH) is a subtype of subarachnoid hemorrhage (SAH) where the bleeding source remains unclear. It is generally associated with a benign clinical course compared to other SAH types. This study retrospectively analyzed 198 pmSAH patients admitted between January 2019 and December 2023, along with 137 non-perimesencephalic non-aneurysmal subarachnoid hemorrhage (npmSAH) and 198 aneurysmal SAH patients as controls. Results showed that pmSAH incidence accounted for approximately 5.6% of all SAH cases and 59.1% of non-aneurysmal SAH cases. pmSAH patients exhibited milder clinical severity, with higher Glasgow Coma Scale scores and lower Hunt-Hess grades compared to aSAH and npmSAH patients. At onset, pmSAH patients were less likely to experience loss of consciousness, incontinence, or convulsions. They also had fewer complications, shorter hospital stays, and a lower proportion of poor prognosis. Multivariate logistic regression identified complications and Hunt-Hess grade as independent risk factors for poor prognosis in pmSAH. In conclusion, pmSAH patients demonstrated relatively mild clinical courses, fewer complications, and better prognosis. However, occasional occurrences require further attention.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 71-77"},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989306","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":"Contribution of vestibular afference to estimation of centre of mass state for stabilization of walking differs between anteroposterior and mediolateral directions","authors":"Yiyuan C. Li ,&nbsp;Koen K. Lemaire ,&nbsp;Sjoerd M. Bruijn ,&nbsp;Simon Brumagne ,&nbsp;Jaap H. van Dieën","doi":"10.1016/j.neuroscience.2025.08.066","DOIUrl":"10.1016/j.neuroscience.2025.08.066","url":null,"abstract":"<div><div>Walking without falling requires correcting the deviations of the centre of mass (CoM) trajectory relative to the base of support. This process is partially under feedback control. We investigated whether vestibular afference contributes to estimating CoM state to stabilize walking. We disturbed the vestibular afference by electrical vestibular stimulation (EVS), which typically leads to responses coherent with the stimulus and directed opposite to movement direction encoded by the induced vestibular signal. With the head facing forward, EVS induces mediolateral perturbations, which shift into the anteroposterior direction when the head is turned sideward in standing. Thirteen participants walked on a treadmill for 8  min at 78 steps/min and 2.8 km/h in four conditions, defined by the presence of EVS and head orientations (facing forward or leftward). A linear regression between the CoM state, described as the extrapolated CoM, and the delayed ground reaction force (GRF) was fitted, which was used to identify a ‘feedback model’. Negative correlations were found in all conditions, indicating that delayed compensatory actions are modulated to correct the deviation of CoM state. EVS significantly increased the magnitude of the GRF not predicted by the XCoM, i.e. the residual error of the feedback model. Contrary to our hypothesis, the increase in the anteroposterior direction was significantly smaller when walking with head facing leftward than when facing forward. Our findings indicate that vestibular afference contributes to estimating CoM state for walking stabilization in the mediolateral direction, but they do not support such a contribution for the anteroposterior direction.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 40-49"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932434","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":"Intranasal nanoparticle therapy for arsenic-induced neurotoxicity: Restoring IGF-1 signaling and advancing translational neuroprotection","authors":"Nourhan Elsayed ,&nbsp;Jhi Biau Foo","doi":"10.1016/j.neuroscience.2025.08.065","DOIUrl":"10.1016/j.neuroscience.2025.08.065","url":null,"abstract":"<div><div>Insulin-like growth factor-1 (IGF-1) is a critical neurotrophic hormone involved in central nervous system (CNS) development and neuroprotection, primarily through its regulation of the PI3K/AKT and MAPK/ERK signaling pathways. Chronic exposure to arsenic, a prevalent environmental neurotoxin, has been increasingly associated with IGF-1 signaling disruption, resulting in oxidative stress, neuronal apoptosis, cognitive dysfunction, and progressive neurodegeneration. This review provides a comprehensive analysis of the mechanistic interplay between arsenic-induced neurotoxicity and IGF-1 pathway impairment, emphasizing the molecular and functional consequences on brain health. To address these challenges, we explore emerging nanotechnological strategies, specifically, nanoparticle (NP)-based drug delivery systems, as promising therapeutic tools. Particular attention is given to intranasal delivery platforms such as liposomes, solid lipid NPs, nanoemulsions, and cubosomes that encapsulate both synthetic and natural neuroprotective agents. Notably, this review presents, for the first time in this context, a comparative evaluation of these NP systems, highlighting their respective advantages, limitations, and brain-targeting capabilities. In addition to synthesizing preclinical evidence, we critically assess translational barriers to clinical implementation, including regulatory hurdles, scalability, and long-term safety considerations. By integrating insights from neurotoxicology, nanomedicine, and translational neuroscience, this review offers a novel perspective on counteracting arsenic-induced cognitive decline and proposes a potential paradigm shift in the treatment of environmentally driven neurodegenerative disorders.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 107-124"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993053","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":"TREM2 mediates parkinsonism-like neurodegeneration in carbon disulfide-induced neurotoxicity","authors":"Liu Zhidan ,&nbsp;Li Xianjie ,&nbsp;Shan Shulin ,&nbsp;Jia Qiang ,&nbsp;Lou Jianwei ,&nbsp;Song Fuyong","doi":"10.1016/j.neuroscience.2025.08.063","DOIUrl":"10.1016/j.neuroscience.2025.08.063","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and aggregation of α-Synuclein (α-Syn). While both genetic and environmental factors are implicated in PD pathogenesis, the mechanisms underlying neurodegeneration induced by environmental toxins and associated genetic responses remain largely unknown. Recently, triggering receptor expressed on myeloid cells 2 (TREM2) has been proven to be a critical mediator of toxin-induced motor neuron degeneration. Using GWAS data, this study employed Mendelian randomization analysis and revealed a significant association between elevated serum TREM2 levels and increased risk of secondary PD. Further experiments used 20 male wild-type mice and 20 male <em>TREM2 KO</em> mice exposed to corn oil or carbon disulfide (an environmental toxin associated with PD), respectively, revealed that TREM2 acts as a molecular switch, amplifying environmental neurotoxicity through the excessive activation of microglia. In contrast, <em>Trem2 KO</em> exhibited pronounced neuroprotective effects, including reduced α-Syn aggregation in the substantia nigra, alleviated nigral neuronal structural damage, diminished neuroinflammation, and improved motor coordination in mice. Finally, protein docking and interaction analysis verified that TREM2 recognizes α-Syn and participates in PD-related pathological events, including neuroinflammation and mitochondrial damage. In summary, the present study identifies TREM2 as a pivotal mediator in environmentally induced Parkinsonian syndromes, providing novel insights into the mechanisms underlying neurodegeneration due to environmental toxin exposure and offering potential targets for precise therapeutic interventions.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 50-59"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989305","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":"Postnatal Zika virus infection increases seizure susceptibility and disrupts cortical organization and GABAergic interneuron positioning in mice","authors":"Michele Ramos Lourenço ,&nbsp;Raissa Rilo Christoff ,&nbsp;Tailene Rabello ,&nbsp;Lidia Gomes Paúra ,&nbsp;Jéssica C.C.G. Ferreira ,&nbsp;Fabio A. Mendes ,&nbsp;Luiza M. Higa ,&nbsp;Maria Bellio ,&nbsp;Amilcar Tanuri ,&nbsp;Henrique Rocha Mendonça ,&nbsp;Patricia P. Garcez","doi":"10.1016/j.neuroscience.2025.08.026","DOIUrl":"10.1016/j.neuroscience.2025.08.026","url":null,"abstract":"<div><div>Zika virus (ZIKV) infection during gestation causes fetal brain abnormalities such as microcephaly, cortical malformations, and motor defects. Infected infants often develop epilepsy and other neurodevelopmental impairments later in life. Animal models show that ZIKV infection leads to seizures and neuroinflammation, disrupting brain development and function. While much research focuses on glutamatergic neuronal development, little is known about how ZIKV affects the development of GABAergic interneurons, which are crucial for brain circuitry and implicated in epilepsy. Here, we aim to evaluate the cortical GABAergic interneuron organization at the cerebral cortex during postnatal development until adulthood using a mouse model of ZIKV perinatal infection. ZIKV infection increases susceptibility to hyperthermic seizures in infected pups. Also, viral infection increases c-Fos, a marker of neuronal activity in the cerebral cortex, accompanied by cortical disorganization with dysmorphic cells observed in HE staining. Additionally, ZIKV disrupts the positioning of GABAergic interneurons, with a different distribution of calbindin-positive and parvalbumin-positive cells at P60 in infected mice, compared to the control. Taken together, these results suggest that ZIKV infection may contribute to impaired cortical inhibition and increased hyperthermic seizure risk.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 125-132"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993069","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":"Impact of endogenous vasohibin 1 and vasohibin 2 gene expression on ferroptosis in a mouse cerebral infarction model","authors":"Hongming Sun,&nbsp;Xinran Hu,&nbsp;Zhihong Bian,&nbsp;Haibo Yu,&nbsp;Yuting Bian,&nbsp;Ricardo Satoshi Ota-Elliott,&nbsp;Hangping An,&nbsp;Zhihong Liu,&nbsp;Ryuta Morihara,&nbsp;Yusuke Fukui,&nbsp;Hiroyuki Ishiura,&nbsp;Toru Yamashita","doi":"10.1016/j.neuroscience.2025.08.061","DOIUrl":"10.1016/j.neuroscience.2025.08.061","url":null,"abstract":"<div><div>The <em>vasohibin 1</em> (<em>Vash1</em>) and <em>vasohibin 2</em> (<em>Vash2</em>) genes, known for their role in regulating angiogenesis, are also implicated in various cellular processes, including ferroptosis, a form of programmed cell death. However, the relationship between the endogenous <em>Vash1</em> and <em>Vash2</em> gene and ferroptosis in ischemic stroke was unknown. In this study, we investigated the function of the endogenous vasohibin genes in ferroptosis in a transient middle cerebral artery occlusion mice model. Motor function, infarct volume, and the expression levels of ferroptosis inhibitor GPX4 and the ferroptosis marker ACSL4 were evaluated with three experimental groups including wild-type (n = 24), <em>Vash1</em> (+/–) mice (n = 24), and <em>Vash2</em> (+/–) mice (n = 24). The cerebral infarct volume of <em>Vash2</em> (+/–) mice was significantly larger than in <em>Vash1</em> (+/–) mice. Compared with the <em>Vash1</em> (+/–) mice, the <em>Vash2</em> (+/–) mice exhibited significantly worse motor recovery and larger infarct volumes 24 h after ischemia–reperfusion. Western blot revealed that these detrimental effects in <em>Vash2</em> (+/–) mice were linked to the downregulated NRF2 and HIF1-α expression. It further demonstrated that the expression level of GPX4 was significantly lower, whereas ACSL4 expression level was significantly higher in the <em>Vash2</em> (+/–) group compared with the <em>Vash1</em> (+/–) group. These findings highlight the distinct roles of <em>Vash1</em> and <em>Vash2</em> in cerebral ischemia. The reduction of <em>Vash1</em> exhibits neuroprotective while reducing the <em>Vash2</em> expression exacerbates ischemic injury through distinct pathways. Targeting regulated <em>Vash1</em> and <em>Vash2</em> expressions may offer novel therapeutic strategies for mitigating reperfusion injury.</div><div>.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 170-180"},"PeriodicalIF":2.8,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962508","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":"Hormonal contraceptive use and type matter: Distinct cortisol patterns and cortisol-mood relations","authors":"Ally H. Villeneuve ,&nbsp;Ayeila Z.B. Daneshmend ,&nbsp;Dana A. Jarkas ,&nbsp;Robyn J. McQuaid","doi":"10.1016/j.neuroscience.2025.08.054","DOIUrl":"10.1016/j.neuroscience.2025.08.054","url":null,"abstract":"<div><div>Hormonal contraceptives (HCs) are used by millions of people globally; however, the implications of HC use on mood and neuroendocrine processes are not fully understood. Thus, the main goal of the current investigation was to assess stress, mood, quality of life, and cortisol patterns in individuals who were naturally cycling or using HC. Another goal was to differentiate HC type, assessing relations in combined oral contraceptive (COC) versus progestin-only HC users. Young females (<em>N</em> = 191) in first- and second-year university (<em>M_age</em> = 19.02, <em>SD</em> = 1.04) completed online self-report stress and mood questionnaires and provided samples for diurnal cortisol determination. When comparing HC users to naturally cycling females, no differences were found for stress, mood or diurnal cortisol patterns. However, distinct correlations were found between cortisol profiles and mood outcomes. This may indicate that the linkages between elevated mood symptoms and cortisol are dysregulated among HC users. When considering HC type, quality of life was higher in COC users compared to naturally cycling females; however, this was not found in progestin-only users. Progestin-only users were more likely to self-report a mental health diagnosis, an effect also significant in an independent replication sample of young females (<em>N</em> = 411; <em>M_age</em> = 19.34, <em>SD</em> = 2.15). Moreover, in the replication sample, plasma cortisol levels were lower among progestin-only users compared to COC users. This study contributes to a growing body of evidence that highlights complex relationships between HC use, mood outcomes, and neuroendocrine functioning, and emphasizes that type of HC matters.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 158-169"},"PeriodicalIF":2.8,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962577","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":"Neuroinflammation in long COVID: the role of the Val16Ala polymorphism of SOD2 and cognitive impairment","authors":"Kimberly Fontoura do Nascimento ,&nbsp;Eduardo Felipe Alchieri ,&nbsp;Carolina Sanguinet Sanson ,&nbsp;Maria Eduarda Andrade Cavalli ,&nbsp;Yuri Augusto Moreira Pena ,&nbsp;Ighor Senji Okumura Tioda ,&nbsp;Laura Eduarda de Oliveira ,&nbsp;Josi Arend ,&nbsp;Marta M.M.F. Duarte ,&nbsp;Clóvis Paniz ,&nbsp;Mauro Schneider Oliveira ,&nbsp;Ana Flavia Furian ,&nbsp;Luiz Fernando Freire Royes ,&nbsp;Michele Rechia Fighera","doi":"10.1016/j.neuroscience.2025.08.047","DOIUrl":"10.1016/j.neuroscience.2025.08.047","url":null,"abstract":"<div><div>Long COVID (LC) includes persistent behavioral and cognitive deficits, impacting quality of life. Neuroinflammation plays a key role in these alterations, with genetic factors influencing susceptibility. The MnSOD Val16Ala SNP is associated with neuroinflammation and cognitive dysfunction, but its role in LC remains unclear. This study investigated the relationship between the SOD2 Val16Ala polymorphism and neurocognitive alterations in young adults post-SARS-CoV-2 infection. Neurocognitive performance was assessed using the Neupsilin test in individuals with and without prior COVID-19. Blood samples were collected for the quantification of cytokines (IL-1, IL-6, TNF-α, and IFN-γ) and for the genotyping of the SOD2 Val16Ala polymorphism. The COVID-19 group showed worse cognitive performance and higher cytokine levels than controls, particularly in memory and executive function. Val allele carriers (Val/Ala and Val/Val) exhibited increased pro-inflammatory cytokine levels compared to Ala/Ala carriers. These findings suggest a potential interaction between genetic susceptibility and inflammatory response in post-COVID neurocognitive alterations. Young adults post-COVID-19 presented an exacerbated neuroinflammatory response, likely influencing cognition. The presence of the Val allele was associated with greater susceptibility to inflammatory events, suggesting a genetic component in LC-related neurological dysfunction. These results reinforce the role of neuroinflammation in LC and highlight the importance of genetic factors in determining cognitive outcomes. Understanding these mechanisms may help identify individuals at higher risk and support future therapeutic strategies.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 418-428"},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962547","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":"Recurrent spaced concussions in adolescent rats disrupt cortical dopaminergic markers and induce behavioral hyperactivity and impaired object location memory","authors":"Douglas Buchmann Godinho ,&nbsp;Leandro Machado Severo Feiteiro ,&nbsp;Gustavo Cassol ,&nbsp;Rafael Parcianello Cipolat ,&nbsp;Getulio Nicola Bressan ,&nbsp;Roselei Fachinetto ,&nbsp;Mauro Schneider Oliveira ,&nbsp;Ana Flavia Furian ,&nbsp;Michele Rechia Fighera ,&nbsp;Luiz Fernando Freire Royes","doi":"10.1016/j.neuroscience.2025.08.043","DOIUrl":"10.1016/j.neuroscience.2025.08.043","url":null,"abstract":"<div><div>Repeated concussions during critical stages of brain development can lead to lasting neural and behavioral changes. This study characterized the consequences of recurrent, spaced concussions using a clinically relevant adolescent Wistar rat model. Male rats were subjected to ten spaced concussions via a weight-drop model during adolescence (P42–P73) and subsequently underwent neurobehavioral, neurochemical, and histological analysis. Behaviorally, the concussion protocol induced hyperactivity in the open-field test and produced specific deficits in the Novel Object Location task; in contrast, performance was unimpaired in the Novel Object Recognition and Barnes Maze tests. These behavioral outcomes were accompanied by disruptions to cortical dopaminergic and GABAergic systems, including reduced dopamine D2 receptor levels, lower monoamine oxidase-A activity, and decreased brain-derived neurotrophic factor (BDNF) and increased gamma-aminobutyric acid decarboxylase 67 (GAD67) expression. Concurrently, glial fibrillary acidic protein (GFAP) expressions were elevated in specific corticolimbic regions. Importantly, these alterations occurred without severe injury markers, such as loss of consciousness or albumin extravasation. Our findings demonstrate that spaced concussive events during adolescence are sufficient to produce distinct behavioral and neurochemical deficits. This work highlights dopaminergic dysfunction as a key etiological factor and potential therapeutic target for impairments following repeated concussions in the developing brain.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 28-39"},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926261","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}