Brain Research最新文献

{"title":"From the past to the future: The influence of early social deprivation on learning and behavioral development through programming","authors":"Caio Matheus Santos da Silva Calado ,&nbsp;Raul Manhães-de-Castro ,&nbsp;Henrique José Cavalcanti Bezerra Gouveia ,&nbsp;Renata Maria Toscano Barreto Lyra Nogueira ,&nbsp;Vanessa da Silva Souza ,&nbsp;Augusto Vagner Soares Martins de Lira ,&nbsp;Samantha Mayra de Araújo Merencio ,&nbsp;Bruno Monteiro Paiva Lima ,&nbsp;Marcelo Valentin Pinto de Oliveira ,&nbsp;Ana Elisa Toscano","doi":"10.1016/j.brainres.2025.149924","DOIUrl":"10.1016/j.brainres.2025.149924","url":null,"abstract":"<div><div>Early life is a critical period for healthy development in mammals, during which social contact plays a central role, being crucial for acquiring adaptive skills. Conversely, adverse experiences such as maternal deprivation and social isolation can produce long-lasting and potentially irreversible effects on cognitive and socioemotional abilities. This study investigated the impact of early social deprivation during childhood and adolescence on learning, language, and social skills, and is divided into two parts: a systematic review of rodent models and a narrative review of clinical studies in humans. In phase one, 12,378 articles were identified, of which 55 were included by the eligibility criteria. The findings indicate that maternal deprivation in rodents impairs spatial learning, discrimination, and prosocial behaviors, while increasing anxiety-like behavior and aggression. These effects are exacerbated when deprivation involves complete social isolation from littermates and may persist across generations. In phase two, clinical studies confirm that early social deprivation compromises cognitive development and causes delays in language acquisition and disrupts social functioning. Protective factors, such as stable caregiving and later social reintegration, appear to mitigate some of these outcomes. The findings underscore the profound impact of early social deprivation on brain development and behavior, highlighting the need for preventive and rehabilitative interventions.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149924"},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of alpha/theta neurofeedback on mood, anxiety, emotion regulation and trait impulsivity","authors":"Linda Dinc ,&nbsp;Daniel Rybski ,&nbsp;Jessica Dineen","doi":"10.1016/j.brainres.2025.149943","DOIUrl":"10.1016/j.brainres.2025.149943","url":null,"abstract":"<div><div>Previous research showed that neurofeedback improved mood, anxiety and addiction symptoms and enhanced optimum performance among musicians and artists. Although the alpha/theta protocol was used in some of these studies, the results have been inconsistent, this is in part due to limited or no use of mock-feedback control groups and the focus being on mostly clinical samples. The current study aimed to comprehensively assess the effects of alpha/theta neurofeedback on state and trait emotions. Twenty-five participants who met the criteria for at least moderate anxiety on GAD-7 were assigned to either real or mock-feedback and completed nine sessions over five weeks. Pre and post emotion dysregulation (DERS-SF), trait impulsivity (SUPPS-P), anxiety (GAD-7) was measured at S1 and S9, and state mood (PANAS) was assessed pre and post each session. The results revealed significant reduction in anxiety among real feedback group at post-S9, while the state negative mood improved for both groups at post sessions. There was no significant change in emotion dysregulation or trait impulsivity from pre to post neurofeedback. Real feedback group showed significant within session increase in their theta/alpha ratio while there was no significant difference between sessions. Overall, the findings suggest that alpha/theta neurofeedback is an effective intervention for anxiety and improves state mood but does not lead to change in traits such as emotion-based impulsivity and emotion dysregulation. This is the first study to comprehensively assess alpha/theta neurofeedback training on different dimensions of emotions in a simulation-controlled design, limitations and implications are discussed.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149943"},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture pretreatment alleviates cerebral Ischemia-Reperfusion-Induced intestinal barrier injury and neuroinflammation via inhibition of the TLR4/NLRP3 inflammasome pathway in rats","authors":"Tao Ye ,&nbsp;Ning Zhang ,&nbsp;Xiaoqin Tan ,&nbsp;Qiqi Zha ,&nbsp;Chunyan Chen ,&nbsp;Fei Quan ,&nbsp;Wanxia Cen ,&nbsp;Xuemei Wu","doi":"10.1016/j.brainres.2025.149944","DOIUrl":"10.1016/j.brainres.2025.149944","url":null,"abstract":"<div><div>This study investigates the protective effects and mechanisms of electroacupuncture (EA) pretreatment on intestinal barrier dysfunction following cerebral ischemia–reperfusion injury (CIRI), with a focus on the TLR4/NLRP3 inflammasome pathway. A middle cerebral artery occlusion (MCAO) rat model was established, with groups divided into Sham, ischemia–reperfusion (I/R), and EA pretreatment (I/R + EA). Neurological function and intestinal pathology were dynamically assessed at 2, 24, and 72 h post-reperfusion. Results demonstrated that EA pretreatment significantly attenuated CIRI-induced intestinal mucosal edema, inflammatory infiltration, and fibrosis, while improving neurological deficits. Mechanistically, EA pretreatment suppressed the TLR4/NF-κB/NLRP3 inflammasome axis, reducing pro-inflammatory cytokines (IL-1β, IL-18) and enhancing anti-inflammatory factors (TGF-β1, IL-4) and the antioxidant protein TRX1. Concurrently, it lowered plasma levels of lipopolysaccharide (LPS), diamine oxidase (DAO), and D-lactate, restoring intestinal epithelial tight junctions. 16S rDNA sequencing revealed that EA pretreatment reversed CIRI-induced gut microbiota dysbiosis, inhibiting pathogenic Escherichia-Shigella proliferation and rebalancing the Firmicutes/Bacteroidetes ratio. This study firstly identifies that EA pretreatment establishes a “neuro-immune-microbial” protective network through spatiotemporal modulation of the TLR4/NLRP3 pathway and microbiota interactions, providing a novel theoretical foundation for the “brain-gut co-protection” strategy in ischemic stroke therapy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149944"},"PeriodicalIF":2.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabinoid agonist, WIN 55,212-2, increases in vivo paired-pulse facilitation, long-term potentiation, and Arc expression in the dentate gyrus","authors":"Felicha T. Candelaria-Cook ,&nbsp;Derek A. Hamilton","doi":"10.1016/j.brainres.2025.149937","DOIUrl":"10.1016/j.brainres.2025.149937","url":null,"abstract":"<div><div>The endogenous cannabinoid system in the hippocampus has the potential to modulate synaptic transmission, including short and long term plasticity, by acting as retrograde messengers. The present study evaluated the effects of WIN 55,212-2, a potent cannabinoid agonist, on paired-pulse facilitation (PPF) and long-term potentiation (LTP) in the dentate gyrus <em>in vivo</em>. WIN 55,212-2 (10  μg/μL; 0.5  μL volume) or vehicle was unilaterally infused into the right dorsal hippocampus of anesthetized rats prior to perforant path stimulation and electrophysiological recordings. Upon completion of physiological recordings, brains were processed for immediate early gene expression (Arc, c-Fos, zif268). WIN 55,212-2 reduced baseline population spike amplitude at high stimulation intensities (500–600 μA), without affecting baseline fEPSP slopes. WIN 55,212-2 also altered fEPSP paired-pulse ratios, suggesting changes in glutamate release probability and GABAergic inhibition. WIN 55,212-2 significantly increased fEPSP slopes following high-frequency stimulation without affecting population spike amplitude, indicating selective enhancement of fEPSPs. Arc expression was significantly elevated in the stimulated dentate gyrus of WIN 55,212-2-treated rats, with no changes in c-Fos or zif268 expression. WIN 55,212-2 may modulate LTP through a combined reduction of glutamate and GABA via feedforward and feedback processes, and may influence baseline and activity-dependent changes via distinct mechanisms. Taken together, these results suggest cannabinoids at high concentration enhance synaptic plasticity mechanisms, which may be important factors driving the effects of cannabinoids on learning and memory.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149937"},"PeriodicalIF":2.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized dose of hydrogen-enriched water with minocycline combination therapy in experimental ischemic stroke","authors":"Zhao Jiang ,&nbsp;Tharun T. Alamuri ,&nbsp;Darren L. Yang ,&nbsp;Tyler Annarino ,&nbsp;Eric R. Muir ,&nbsp;Tim Q. Duong","doi":"10.1016/j.brainres.2025.149940","DOIUrl":"10.1016/j.brainres.2025.149940","url":null,"abstract":"<div><h3>Background</h3><div> <!-->Ischemic stroke remains a leading cause of death and disability worldwide, with limited effective treatments due to the complexity of its pathophysiology. Molecular hydrogen (H₂) and minocycline (M), both possessing anti-inflammatory and antioxidant properties, have shown individual neuroprotective potential in preclinical models. However, the optimal therapeutic dosing of H₂, particularly in combination with other agents, remains undefined.</div></div><div><h3>Objective</h3><div> <!-->This study aimed to (1) determine the dose–response relationship of hydrogen-enriched water in a rat model of transient middle cerebral artery occlusion (MCAO), and (2) evaluate whether optimized H₂ dosing combined with minocycline provides superior neuroprotection compared to H₂ monotherapy.</div></div><div><h3>Methods</h3><div> <!-->Sixty-six male and female Sprague-Dawley rats underwent 60-minute MCAO followed by treatment with varying doses (5–30 mL/kg) of hydrogen-enriched water (3.2 ppm), alone or in combination with minocycline (20 mg/kg). Treatments were administered post-reperfusion as well as on days 1 and 2. Behavioral outcomes (Garcia score) and infarct volumes (TTC staining) were assessed at 7 days post-stroke.</div></div><div><h3>Results</h3><div> <!-->The optimal H₂ dose was 20 mL/kg, which produced the highest Garcia scores and lowest infarct volumes. A dose-dependent effect was observed with a quadratic fit (R² = 0.751 for Garcia scores; R² = 0.289 for lesion volume). Combination therapy with H₂ and minocycline significantly outperformed H₂ monotherapy in both neurological recovery and infarct reduction, with no sex differences observed.</div></div><div><h3>Conclusion</h3><div> <!-->Hydrogen-enriched water shows a dose-dependent neuroprotective effect in experimental ischemic stroke, with 20 mL/kg identified as the optimal dose. Combined therapy with minocycline further enhances outcomes, supporting the potential of dual-agent strategies for improved stroke treatment. These findings provide a foundation for translational development of H₂-based combination therapies in clinical settings.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149940"},"PeriodicalIF":2.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethyl pyruvate shields the brain from oxidative damage: a Keap1-Nrf2-dependent mechanism in subarachnoid hemorrhage","authors":"Mei Zhang,&nbsp;Xiaojiao Deng,&nbsp;Zhenfei Teng,&nbsp;Hai Yu,&nbsp;Zelin Hao,&nbsp;Haisong Xu,&nbsp;Wusi Qiu,&nbsp;Jun Cheng,&nbsp;Jianyue Wu","doi":"10.1016/j.brainres.2025.149939","DOIUrl":"10.1016/j.brainres.2025.149939","url":null,"abstract":"<div><h3>Background</h3><div>Early brain damage (EBI) is a serious consequence of subarachnoid hemorrhage (SAH). It has been demonstrated that ethyl pyruvate (EP) reduces the early brain damage brought on by SAH. This study investigates the role of the kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the protective effects of EP on SAH-induced early brain injury.</div></div><div><h3>Methods</h3><div>In this study, we examined the effects of EP on brain damage in a rat model of SAH, including SAH grading, brain water content measurement, neurological function scoring, reactive oxygen species (ROS) levels, and apoptosis. Additionally, we analyzed the involvement of the Keap1-Nrf2 pathway using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Nrf2 knockdown was performed to assess its impact on the therapeutic effects of EP in SAH.</div></div><div><h3>Results</h3><div>EP treatment significantly alleviated SAH-induced brain damage, including reducing brain water content, ROS levels, and apoptosis, while improving neurological function scores. Furthermore, EP modulated the Keap1-Nrf2 pathway by decreasing Keap1 expression and increasing Nrf2 and HO-1 expression in the brain. Nrf2 knockdown attenuated the protective effects of EP, indicating that Nrf2 activation plays a crucial role in EP’s neuroprotective effects.</div></div><div><h3>Conclusion</h3><div>EP alleviates oxidative stress and neuronal damage following SAH by regulating the Keap1-Nrf2 signaling pathway. These results demonstrate EP’s potential as a treatment approach that shows promise for enhancing patient outcomes in SAH.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149939"},"PeriodicalIF":2.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the potential pathogenesis of migraine using glutamatergic neuron models derived from induced pluripotent stem cells (iPSCs) of migraine patients","authors":"Yueyue Xu ,&nbsp;Yitian Yao ,&nbsp;Li Sun ,&nbsp;Li Chen ,&nbsp;Chenyang Li ,&nbsp;Wenyuan Wang ,&nbsp;Jiajun Yang","doi":"10.1016/j.brainres.2025.149938","DOIUrl":"10.1016/j.brainres.2025.149938","url":null,"abstract":"<div><div>Migraine is a complex neurological disorder influenced by multiple genetic susceptibility factors, yet current animal models fail to fully recapitulate its human-specific pathophysiology. In this study, we explored the potential mechanisms underlying migraine by examining functional abnormalities and molecular dysregulation in glutamatergic neurons derived from induced pluripotent stem cells (iPSCs) of migraine patients. As key excitatory cells in the central nervous system, glutamatergic neurons are implicated in migraine through altered excitability, ion channel dysfunction, and dysregulation of nociceptive signaling molecules. iPSCs from both migraine patients and healthy controls were differentiated into glutamatergic neurons. Electrophysiological properties and sodium and potassium channel functions were assessed using whole-cell patch-clamp recordings. Expression levels of migraine-associated molecules, including P2RX3, calcitonin gene-related peptide (CGRP), and c-Fos, were evaluated via immunofluorescence and quantitative real-time PCR. Dysfunction of glutamatergic neurons, involving ion channel dysregulation and abnormal molecular expression, may be implicated in migraine pathology and may provide potential targets for therapeutic intervention. The iPSC-based model may help to address some limitations of animal studies and offers a potential platform for migraine precision medicine research. As a proof-of-principle study, these findings highlight the feasibility of using iPSC-derived glutamatergic neurons to explore migraine mechanisms. While preliminary, this model may serve as a valuable foundation for future translational and precision medicine research.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149938"},"PeriodicalIF":2.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rutin alleviates lipopolysaccharide-induced neuroinflammation and blood brain barrier dysfunction","authors":"Yuanyuan Meng ,&nbsp;Xingyu Liu ,&nbsp;Ding Ding ,&nbsp;Jingrong Wang ,&nbsp;Jian Mao ,&nbsp;Le Kang ,&nbsp;Lili Cao","doi":"10.1016/j.brainres.2025.149941","DOIUrl":"10.1016/j.brainres.2025.149941","url":null,"abstract":"<div><div>The blood–brain barrier (BBB) plays a pivotal role in safeguarding and sustaining the brain’s microenvironment. Disruption of this barrier is commonly observed in various neurological disorders and is intricately linked with neuroinflammation. Rutin, a natural flavonoid known for its diverse biological activities, has showed protective effects against neuroinflammation. However, its anti-neuroinflammation role and potential to preserve the integrity of the BBB has yet to be fully elucidated. In the present study, we investigated the effects of rutin against lipopolysaccharide (LPS)-induced neuroinflammation and BBB dysfunction. The results showed that rutin pretreatment effectively mitigated LPS-induced BBB disruption and inflammatory changes in the mice brain. Mechanistically, rutin inhibited LPS-induced microglial activation and decreased the production of pro-inflammatory cytokines primarily via the caspase-mediated non-canonical inflammatory signaling pathway. These findings highlight rutin as a promising therapeutic candidate for alleviating neuroinflammation related neurological disorders.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149941"},"PeriodicalIF":2.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The peptide ENSG00000232259-ORF inhibits glioma cell proliferation and migration by promoting autophagy","authors":"Jiaqi Zhang ,&nbsp;Gangao Wei ,&nbsp;Baoshun Du ,&nbsp;Zhenguo Cheng ,&nbsp;Zheying Zhang","doi":"10.1016/j.brainres.2025.149942","DOIUrl":"10.1016/j.brainres.2025.149942","url":null,"abstract":"<div><div>Glioma is a malignant brain tumor in which the lncRNA ENSG00000232259 is significantly upregulated. Bioinformatics predictions suggest that it may encode the polypeptide ENSG00000232259-ORF, but the biological function and mechanisms of this polypeptide in glioma remain unclear. Gene expression and correlation analyses were conducted using the GEPIA database, combined with GetORF to predict the polypeptide-coding potential, and Western blot was employed to validate the expression of ENSG00000232259-ORF. Functional experiments demonstrated that this polypeptide significantly inhibits glioma cell proliferation and migration, as evidenced by CCK8, colony formation, Transwell, and scratch assays, and this effect is independent of its parent lncRNA. Mechanistically, ENSG00000232259-ORF promotes autophagy by upregulating ATG3 expression, manifested by increased levels of LC3B and decreased P62. Knockdown of ATG3 reversed the inhibitory effects of the polypeptide on cell proliferation and migration. These findings reveal that ENSG00000232259-ORF suppresses glioma progression by activating the autophagy pathway, providing a potential new target for tumor therapy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149942"},"PeriodicalIF":2.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational inoculation by the Zika virus causes cognitive impairment and Na+K+-ATPase activity imbalance in frontal cortex of adult male and female Wistar rat’s offspring","authors":"Meirylanne Gomes da Costa ,&nbsp;Adriana Souza dos Santos ,&nbsp;Wellington de Almeida ,&nbsp;Anna Luísa Lothhammer Bohn ,&nbsp;Brenda Katelyn Viegas da Rosa ,&nbsp;Bruna Carolina de Castro Saturnino ,&nbsp;Aline Martins Faustino ,&nbsp;Chris Krebs Danilevicz ,&nbsp;Ana Paula Muterle Varela ,&nbsp;Thais Fumaco Teixeira ,&nbsp;Paulo Michel Roehe ,&nbsp;Osmar Vieira Ramires Júnior ,&nbsp;Angela Terezinha de Souza Wyse ,&nbsp;Lenir Orlandi Pereira","doi":"10.1016/j.brainres.2025.149928","DOIUrl":"10.1016/j.brainres.2025.149928","url":null,"abstract":"<div><div>It has been recently described the Congenital Zika Syndrome (CZS). Children from pregnant women who were infected by the virus have expressed a set of symptoms, particularly involving neurological disorders such as microcephaly. Animal models have been conducted aiming to enhance the knowledge about the CZS and giving support for future studies proposing prevention and treatment for this condition. The aim of the present study was to advance in establishing a rat model of CZS observing the impact of zika inoculation during pregnancy on the cognitive processes and nervous tissue damage in the male and female adult offspring. The results revealed the offspring of the inoculated group had impairment in the working memory and learning revealed by the Morris water maze and the OX-maze task, both cortex-dependent tasks. No changes in the brain volume were observed. In addition, Na⁺,K⁺-ATPase activity decrease in the frontal cortex was identified in the zika group. The impact was observed in both male and female animals. Maternal ZIKV infection did not alter the BDNF levels and its receptor TrkB. In conclusion, it is clearly demonstrated the impaired cognition associated to Na⁺,K⁺-ATPase activity disturbance in cortex, consequent to ZIKV gestational inoculation, during adulthood. These findings contribute to the understanding of Congenital Zika Syndrome (CZS) and provide insights for the development of a rat model of the syndrome, highlighting that its effects persist into adulthood, resulting in permanent impacts on neurodevelopment.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149928"},"PeriodicalIF":2.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}