European Journal of Neuroscience最新文献

{"title":"Reduced Brain Complexity During the Execution of a Sequential Arm Movement Following an Augmented-Feedback-Based Practice: A Multiscale Entropy Analysis.","authors":"Daghan Piskin, Linda Margraf, Matthias Weigelt, Jochen Baumeister","doi":"10.1111/ejn.70729","DOIUrl":"https://doi.org/10.1111/ejn.70729","url":null,"abstract":"<p><p>Motor learning is accompanied by adaptive changes in neural processing, yet the extent to which feedback-based practice alters the complexity of cortical activity during movement execution remains unclear. The present study examined learning-associated changes in brain complexity during the execution of a sequential arm movement following augmented-feedback-based practice. Thirty-eight healthy young adults practiced a sequential arm movement with augmented feedback across five sessions. Cortical activity was recorded with electroencephalography during the first and last practice sessions. Multiscale entropy was used to quantify brain complexity across 50 time scales. Behavioral measures indicated improved movement accuracy and reduced dual-task costs across practice. At the cortical level, a significant global decrease in entropy was observed from the first to the last practice session. Further analyses revealed that the differences were confined to coarse temporal window and midline frontal electrodes Fz and FCz. In addition, changes in coarse-scale entropy at FCz were negatively correlated with reductions in absolute error. Together, the present findings suggest that augmented-feedback-based practice is accompanied by a refinement of cortical complexity during movement execution, particularly in large-scale frontal dynamics. Multiscale entropy may therefore provide a sensitive framework for capturing learning-related neural adaptations that complement conventional electroencephalographic measures and advance the understanding of motor learning at the systems level.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149243856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the Oligodendrocyte Progenitor Cell: One Cell, Many Functions","authors":"Alerie G. de la Fuente","doi":"10.1111/ejn.70676","DOIUrl":"https://doi.org/10.1111/ejn.70676","url":null,"abstract":"<p>Oligodendrocyte progenitor cells (OPCs) are resident progenitors and the largest cycling nonneuronal population of the central nervous system (CNS). For decades, OPCs were defined by a single output—the myelinating oligodendrocyte. However, a growing body of evidence has since revealed a cell whose functions reach well beyond myelin, raising the question of whether the OPC should be regarded as a glial cell type in its own right. In this review I examine a broader repertoire of OPC functions and their relevance to CNS health and disease, alongside myelination, remyelination and myelin maintenance. Beyond forming myelinating oligodendrocytes, OPCs tune myelination to neuronal activity, regulate neural circuits directly, influence the vasculature and blood–brain barrier and act as immune sensors and effectors. These emerging myelin-independent functions establish OPCs as active participants in CNS physiology and pathology rather than a cell defined solely by the oligodendrocytes it produces. Finally, I consider two challenges shared across all these functions and that have, until now, been studied almost exclusively in relation to myelination: OPC heterogeneity and ageing. Whether these noncanonical functions are performed by all OPCs or by distinct subsets and inducible states and how each function is shaped across the lifespan and in pathological contexts, remains unresolved. I propose that addressing these questions is essential to understanding the relevance of these different OPC functions in health and disease.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70676","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Attention and Session Day Jointly Modulate Human Visual Cortical Plasticity","authors":"Patricia Naomi Limon,&nbsp;Anthony Norcia,&nbsp;Ryan Thomas Ash","doi":"10.1111/ejn.70695","DOIUrl":"https://doi.org/10.1111/ejn.70695","url":null,"abstract":"<div>\u0000 \u0000 <p>Visual-evoked potential plasticity (VEPP) is a noninvasive form of cortical neuroplasticity elicited by repeated presentation of high-contrast visual stimuli. In rodent models, stimulus-specific response potentiation (SSRP) effects accumulate across days; however, it remains unclear whether repeated exposure across days influences the magnitude or specificity of potentiation in humans. In addition, visual cortical plasticity may not be determined by experience alone: voluntary attentional deployment selects which inputs are prioritized, and may thereby determine how much a given amount of sensory experience alters cortical excitability. Here, we examined whether covert spatial attention and repeated exposure across days modulate VEPP strength using high-density electroencephalography (EEG) in neurotypical adults. An established VEP modulation paradigm was modified to use steady-state visual evoked potential (SSVEP) stimuli, which we refer to as steady-state visual response potentiation (SSVRP). Pre- and post-induction amplitudes were measured using frequency-tagged (6 and 7.5 Hz) bilateral hemifield contrast-sweep checkerboard steady-state visual evoked potentials (SSVEPs). A 10-min, high-contrast, 2 Hz sign-reversing induction stimulus was presented exclusively to the left hemifield, with the right serving as control. Across two experimental sessions, participants attended either toward or away from the potentiated hemifield during induction. Notably, attention enhanced SSVRP in the first session day but not the second session day, reflecting a significant interaction between attention and session day. Potentiation was significantly greater on the second session day, independent of attention condition. Of note, potentiation occurred in both hemifields despite the potentiating stimulus only being presented in the left hemifield. Our results tentatively suggest that spatial attention and experience jointly modulate human visual cortical plasticity.</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072647","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":"Partial Learning in Human Sound Localization With Asymmetric Ears","authors":"Peter Bremen,&nbsp;Robert F. van der Willigen,&nbsp;A. John van Opstal,&nbsp;Marc M. van Wanrooij","doi":"10.1111/ejn.70685","DOIUrl":"https://doi.org/10.1111/ejn.70685","url":null,"abstract":"<p>The brain computes sound location from auditory spatial cues. Humans and barn owls both localize sounds accurately, yet they rely on fundamentally different cue configurations shaped by their ear anatomy and neural circuitry. In humans, symmetrical ears provide interaural time and level differences (ITD and ILD) for horizontal localization, while vertical localization depends primarily on high-frequency, monaural spectral cues generated by the pinnae. Barn owls, by contrast, possess asymmetrical ears and use binaural cues for both azimuth and elevation. Because auditory pathways are tuned to species-specific cue statistics, it remains unclear whether humans can adapt when binaural level cues are also made informative about elevation. We tested this by fitting human listeners with asymmetric ear molds that disrupted normal spectral cues, introduced elevation-dependent ILDs, and left ITDs unaffected. Participants wore the molds during daily life and were tested with broadband, high-pass, and low-pass noise bursts. Acute mold exposure severely degraded elevation localization, whereas horizontal localization remained largely unaffected. With prolonged exposure, elevation localization improved, but adaptation was limited, variable across listeners, and fluctuated across sessions. Improvement was strongest for broadband sounds. Because broadband and high-pass sounds both contained high-frequency information, this broadband advantage cannot be explained by access to additional spectral cues alone. Instead, it suggests that low-frequency ITDs helped listeners exploit the altered binaural cue structure, including the elevation-dependent ILDs introduced by the molds. These findings show that humans can partially adapt to asymmetric outer-ear acoustics when complementary spatial cues help resolve ambiguity in the altered cue structure.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional Alteration in TRKβ-SHC Isoform as a Neuroprotective Factor for Post-Stroke Memory Outcomes","authors":"Dipanwita Sadhukhan,&nbsp;Raktim Chowdhury,&nbsp;Saranya Roy,&nbsp;Arunima Roy,&nbsp;Shreyosi Maitra,&nbsp;Kartik Chandra Ghosh,&nbsp;Joydeep Mukherjee,&nbsp;Tapas Kumar Banerjee,&nbsp;Subhra Prakash Hui,&nbsp;Saikat Chakrabarti,&nbsp;Arindam Biswas","doi":"10.1111/ejn.70684","DOIUrl":"10.1111/ejn.70684","url":null,"abstract":"<div>\u0000 \u0000 <p>Post-stroke cognitive impairment (PSCI) affects nearly 30% of stroke survivors and substantially limits functional recovery. Brain-derived neurotrophic factor (BDNF)–tropomyosin receptor kinase-<i>β</i> (Trk<i>β</i>) signalling plays an important role in synaptic plasticity and cognitive function; however, the contribution of individual NTRK2/Trk<i>β</i> isoforms to PSCI remains poorly understood. This study investigated (a) isoform-specific NTRK2 mRNA expression, (b) genetic association of the isoform-specific variant rs6559833 with post-stroke cognitive outcomes and (c) DNA methylation patterns potentially regulating NTRK2 expression using blood as primary biosource. Isoform-specific expression was analysed in 50 subjects, rs6559833 was genotyped in 280 ischemic stroke patients, and DNA methylation was assessed in 10 samples using whole-genome bisulfite sequencing. The TRK<i>β</i>-FL expression was significantly reduced in stroke patients compared with healthy controls, whereas TRK<i>β</i>-SHC expression was higher in PSCN individuals than in PSCI patients. The latter showed positive correlation with MEK2 expression and memory performance. The ‘TT’ genotype of the rs6559833 variant showed marginal associations with post-stroke memory status and overall BMSE scores (<i>p</i> = 0.0442 and 0.0488, respectively). Furthermore, hypermethylation was observed within the NTRK2 gene body and in genes encoding its splicing regulators, whereas no evident difference in promoter methylation was observed. Collectively, these findings suggest that Trk<i>β</i>-SHC expression may be associated with preserved cognitive function after stroke and indicate a potential relationship between isoform-specific NTRK2 expression, genetic regulation and cognitive outcomes in PSCI.</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012163","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":"Baseline Dynamics and Sleep Loss–Driven Changes of Electrocorticographic Aperiodic Properties Are Altered in Mice Lacking Neuroligin-2","authors":"Tanya Leduc,&nbsp;Janine El Helou,&nbsp;Erika Bélanger-Nelson,&nbsp;Clément Bourguignon,&nbsp;Jean-Marc Lina,&nbsp;Valérie Mongrain","doi":"10.1111/ejn.70665","DOIUrl":"10.1111/ejn.70665","url":null,"abstract":"<p>Spectral power decay (1/<i>f</i>^<i>β</i>) of cortical activity has long been considered of low relevance to the understanding of brain function (e.g., associated with background noise of neuronal activity). However, growing literature suggests that it can reflect optimized spatiotemporal organization of neuronal activity across the cortex serving both cognition and behavior. Thus, clarifying the mechanisms underlying the regulation of this network property could have numerous impacts for the neuroscience field as well as for patients suffering from various neurological disorders with cognitive deficits linked to alterations in brain power decay properties. Using a constitutive knockout mouse and a multifractal wavelet-leaders formalism, we here investigated the involvement of the synaptic adhesion molecule Neuroligin-2, which shapes synaptic inhibition and associates with neurodevelopmental diseases, in modulating spectral power decay properties of the electrocorticographic signal (i.e., the most prominent Hurst exponent “Hm” and its local “Dispersion”). Knockout mice showed increased Hm values across all wake and sleep states together with amplified daily dynamics during wake and paradoxical sleep, and increased Dispersion specifically for slow-wave sleep in comparison with wild-type littermates. Following a 6-h sleep deprivation, Hm daily variations were more altered in knockout mice than controls for wake and paradoxical sleep, but less affected for slow-wave sleep. Importantly, mutant mice display hypersynchronized epileptic-like electrocorticographic events, which were characterized by further increases in Hm and Dispersion. These findings provide support for the involvement of Neuroligin-2 in shaping 1/<i>f</i>^<i>β</i> cortical activity properties and bring perspectives, notably, for neurodevelopmental conditions.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Optic Flow on Electrocortical Dynamics During Walking and Stepping Over Virtual Obstacles","authors":"Marco A. Bühler,&nbsp;Joyce Fung,&nbsp;Anouk Lamontagne","doi":"10.1111/ejn.70694","DOIUrl":"10.1111/ejn.70694","url":null,"abstract":"<p>Successful obstacle avoidance relies on complex visuomotor processes. Although optic flow provides critical information about self-motion and object motion, the neural mechanisms underlying its role during obstacle avoidance remain largely unexplored. To address this gap, we developed a treadmill-based virtual reality paradigm to investigate cortical dynamics during obstacle avoidance performed with and without optic flow. Accordingly, 24 healthy adults walked on a treadmill and stepped over virtual obstacles in two environments: one with optic flow (textured walls/ceiling) and one without. Electroencephalography data were recorded, decomposed with independent component analysis, and clustered within the sensorimotor, parietal, and occipital regions. Time-frequency power was compared across conditions in the theta, alpha, and beta bands. Results revealed transient theta synchronizations shortly after obstacle presentation and before obstacle clearance were observed in all regions and conditions, together with sustained alpha/beta desynchronizations throughout the planning phase. Optic flow enhanced pre-obstacle alpha desynchronizations and uniquely induced sustained occipital theta synchronization in the same period. These modulations in electrocortical activity in the optic flow condition before obstacle presentation likely reflect responses associated with self-motion, whereas its persistence after obstacle presentation suggests a shared contribution of self- and object-motion processing. Sensorimotor alpha power decreased after obstacle presentation, indicating increased engagement in motor planning. Together, these findings demonstrate that optic flow shapes electrocortical dynamics during obstacle avoidance by eliciting distinct neural signatures associated with visual motion processing and motor planning.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic Mosaicism of the Brain: The Functional Implications of Post-Zygotic Mutations to Neural Circuits","authors":"Maher Abdulrazzaq Al-Hakeem,&nbsp;Yasir Qasim Almajidi,&nbsp;Samer Saleem Alshkarchy,&nbsp;Ali Kamil Kareem,&nbsp;Roopashree Rangaswamy,&nbsp;Zahraa Khudhair Al-Khafaji,&nbsp;Priya Priyadarshini Nayak,&nbsp;Kattela Chennakesavulu,&nbsp;Renu Sharma,&nbsp;Wesam R. Kadhum","doi":"10.1111/ejn.70689","DOIUrl":"https://doi.org/10.1111/ejn.70689","url":null,"abstract":"<div>\u0000 \u0000 <p>The human brain is a genomic mosaic shaped by post-zygotic mutations that accumulate from the earliest embryonic divisions through aging. This review synthesizes current evidence on the origins, detection, functional consequences and disease relevance of neural somatic mosaicism. We find that somatic variants—including single-nucleotide variants, copy-number variations, mobile element insertions, structural rearrangements and aneuploidies—arise through distinct molecular mechanisms such as replication errors, oxidative stress, defective DNA repair and transposable element activity, each leaving characteristic mutational signatures. The developmental timing of mutations is the primary determinant of their clonal distribution and functional impact: early mutations generate widespread clones, whereas later events produce localized or single-cell mosaics. We demonstrate that even small populations of mutant neurons can disrupt network dynamics when key signalling pathways are affected, as shown in mTOR-related cortical malformations where non-cell-autonomous mechanisms drive epileptogenesis. Our analysis reveals that somatic mosaicism provides a unifying explanation for diverse neurological conditions, from focal epilepsies and neurodevelopmental disorders to late-onset neurodegenerative diseases, including mechanisms invisible to conventional blood-based genetic testing. We conclude that understanding the brain as a dynamic mosaic of billions of distinct genomes—rather than a single-genome organ—is essential for accurate disease modelling, diagnostics and the development of targeted therapies.</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994428","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":"Time-Dependent Enhancement of Motor Dexterity and Cerebellar Function via Premotor–Cerebellar Associative Stimulation","authors":"Kazuki Tanaka,&nbsp;Atsushi Shima,&nbsp;Erika Omae,&nbsp;Miyabi Toriyama,&nbsp;Tomoaki Miyake,&nbsp;Masako Yamada,&nbsp;Yedi Cao,&nbsp;Tatsuya Mima,&nbsp;Satoko Koganemaru","doi":"10.1111/ejn.70688","DOIUrl":"10.1111/ejn.70688","url":null,"abstract":"<div>\u0000 \u0000 <p>Paired associative stimulation (PAS) techniques are key to understanding neuromodulation and plasticity. Because of the tight interconnections between the cerebral and cerebellar cortices, noninvasive cerebro-cerebellar associative stimulation may enhance cerebellar function; however, this has not been studied in humans. This study investigated whether PAS of the cerebellar hemisphere and premotor cortex (PMC) modulates human cerebellar function in a time-dependent manner. The inclusion criteria were as follows: right-handedness and no history of brain disease. Cerebellar-target PAS was performed by repeating paired stimuli on the left cerebellar hemisphere preceded by the right PMC using interstimulus intervals (ISI) of 5, 20, or 40 ms on three different days. Cerebellar brain inhibition (CBI) and motor dexterity (9-Hole Peg Test and line-tracing tests using the left hand) were evaluated. Twenty-three healthy volunteers aged 20–29 years participated in this study. The CBI of the left cerebellum showed significant enhancement after cerebellar-target PAS with an ISI of 20 ms (CBI-3, <i>p</i> = 0.0031; CBI-5, <i>p</i> = 0.0006; and CBI-10, <i>p</i> = 0.0052) and a significant decrease after an ISI of 5 ms. The performance time on the 9-Hole Peg Test and line tracing tests decreased after an ISI of 20 ms and increased after an ISI of 5 ms. Cerebellar-target PAS with an ISI of 20 ms targeting the left cerebellum improved motor dexterity in the left hand. The effects of cerebellar-target PAS depend on the stimulation interval, which could be a potential therapeutic approach for the neurorehabilitation of patients with cerebellar disorders.</p>\u0000 <p><b>Study Registration:</b> jRCT1052210071</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988656","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":"Neuroprotective Effect of Morin Against Chemical-Induced Neurotoxicities and Neurodegenerative Disease Models","authors":"Bidemi Emmanuel Ekundayo,&nbsp;Motunrayo Comfort Ekundayo,&nbsp;Sunday Ayodele Alonge,&nbsp;Blessing Ariyo Obafemi,&nbsp;Tajudeen Olabisi Obafemi,&nbsp;Sogolo Lucky Lebelo,&nbsp;Monde McMillan Ntwasa","doi":"10.1111/ejn.70692","DOIUrl":"10.1111/ejn.70692","url":null,"abstract":"<div>\u0000 \u0000 <p>Morin (3,5,7,2′,4′-pentahydroxyflavone) is a dietary flavonol with broad neuroprotective, anti-inflammatory, and antioxidant actions across central and peripheral nervous system models. This synthesis consolidates evidence from in vitro and rodent studies—covering neurodegenerative proteinopathies (Alzheimer's, Parkinson's, and Huntington's), neuropathic pain, epilepsy, stress- and schizophrenia-like phenotypes, and chemo-/toxicant-induced neurotoxicity—to evaluate morin's consistent benefits on survival, motor/cognitive performance, and biochemical normalization. Morin mitigated neurotoxicity induced by doxorubicin, ifosfamide, vincristine, acrylamide, heavy metals, and endocrine disruptors. Context-specific effects included modulation of disease-defining pathways (<i>GSK3β</i>/CDK5, mTORC1, PARP, and AMPK–ULK1–TFEB), microglial polarization, and normalization of neurotransmission (dopamine, GABA, 5-HT, and reduced AChE). Core mechanisms included the following: restoration of redox and mitochondrial homeostasis via <i>Nrf2</i>/HO-1 activation; replenishment of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH); decreased reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO); and preserved mitochondrial potential/fusion; suppression of innate immune and inflammasome signaling through downregulation of TLR4/NF-κB and ERK–p65, reduced TNF-α, IL-1β/IL-6, iNOS/COX-2; inhibition of NLRP3/caspase-1; and rebalancing of cell-death programs (↓<i>Bax</i>/caspase-3, ↑<i>Bcl-2</i>; attenuation of RIPK1/RIPK3/MLKL-mediated necroptosis). Formulation strategies (intranasal microemulsions, pluronic micelles, and more soluble derivatives) have enhanced brain exposure and efficacy, but translation now warrants optimized delivery, pharmacokinetic–pharmacodynamic mapping, target engagement biomarkers, and rigorously controlled trials to define dose, route, and indications as adjunctive to standard care in neurodegeneration, neuropathic pain, and toxicant-related brain injury. Collectively, morin emerges as a multitarget neuroprotective scaffold with reproducible functional and mechanistic benefits.</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982437","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}