Camilla W. Pretzel, Hevelyn S. Moraes, Mariana L. Müller, Kimberly Fontoura, Rossano S. Menezes, Julia Canzian, Rodrigo E. Barreto, Cassio M. Resmim, Barbara D. Fontana, Denis B. Rosemberg
{"title":"GBR 12909, a Selective Dopamine Transporter Inhibitor, Differentially Modulates Affective, Exploratory and Cognitive Domains in Zebrafish","authors":"Camilla W. Pretzel, Hevelyn S. Moraes, Mariana L. Müller, Kimberly Fontoura, Rossano S. Menezes, Julia Canzian, Rodrigo E. Barreto, Cassio M. Resmim, Barbara D. Fontana, Denis B. Rosemberg","doi":"10.1111/ejn.70651","DOIUrl":"https://doi.org/10.1111/ejn.70651","url":null,"abstract":"<p>Dopamine plays an important role in several biological functions, such as reward, movement regulation and cognition. Physiological alterations in dopamine transporter (DAT) are related to psychiatric conditions, including bipolar disorder (BD), a condition characterized by intense shifts in mood, behaviour and energy, alternating between manic and depressive states. Administration of GBR 12909, a selective dopamine reuptake inhibitor, has been considered a suitable model to assess BD-related phenotypes, yet the integration of anxiety-like, despair-like, cognitive and spatiotemporal behavioural dimensions has not been systematically evaluated. Here, we evaluated the acute behavioural effects of GBR 12909 using a multidomain behavioural assessment in adult zebrafish. Fish received a single intraperitoneal administration of GBR 12909 (15 mg/kg) and 30 min after, were challenged to the open field test (OFT), light–dark test (LDT), shallow water test (SWT) and Free Movement Pattern Y-Maze (FMP Y-Maze). GBR 12909-treated zebrafish exhibited increased time in homebase during OFT, prominent scototaxis and hyperactivity in LDT, increased immobility and hypolocomotion in SWT, along impaired cognitive flexibility and stereotypical behaviours in the FMP Y-maze. These data reflect affective and cognitive disturbances consistent with dopaminergic overstimulation that triggers manic- and depressive-like phenotypes, thereby recapitulating behavioural phenotypes relevant to multiple domains affected in BD. Collectively, our findings support that GBR12909 elicits dopaminergic-driven behavioural phenotypes relevant to multiple domains of BD, providing a translational model for studying the neurobiological bases of DAT inhibition across distinct behavioural domains.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783901","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}
Ashmeet Jolly, Aura Yli-Savola, Elmo P. Pulli, Essi Saloranta, Henry Railo, Harri Merisaari, Ekaterina Saukko, Eero Silver, Venla Kumpulainen, Anni Copeland, Hasse Karlsson, Linnea Karlsson, Niina Junttila, Elina Mainela-Arnold, Jetro J. Tuulari
{"title":"Structural Brain Correlates of Speech Disfluency in Early Childhood: A Dimensional Analysis in a Population-Based Cohort","authors":"Ashmeet Jolly, Aura Yli-Savola, Elmo P. Pulli, Essi Saloranta, Henry Railo, Harri Merisaari, Ekaterina Saukko, Eero Silver, Venla Kumpulainen, Anni Copeland, Hasse Karlsson, Linnea Karlsson, Niina Junttila, Elina Mainela-Arnold, Jetro J. Tuulari","doi":"10.1111/ejn.70652","DOIUrl":"https://doi.org/10.1111/ejn.70652","url":null,"abstract":"<p>Most neuroimaging studies of speech disfluency have compared individuals who stutter with fluent controls. However, treating speech disfluency as a continuous, dimensional trait offers new insights into the neural basis of fluency during early childhood. We investigated whether naturally occurring variation in speech disfluency is associated with grey matter structure in a population-based sample of 5-year-old children (<i>N</i> = 120; 65 M, 55 F). Disfluency was derived from audio and video-recorded conversational speech samples transcribed and coded using the Ambrose and Yairi classification into stuttering-like disfluencies (SLDs) and other disfluencies (ODs). T1-weighted magnetic resonance imaging data were analyzed using voxel-based morphometry and complemented by surface-based measures of cortical thickness and surface area (FreeSurfer). Whole brain voxel-wise regression tested associations between grey matter and disfluency while adjusting for age, sex, handedness, and maternal education, with additional robustness checks (including intracranial volume adjustment and alternative SLD operationalizations). Higher SLDs were positively correlated with regional grey matter volume primarily in the frontal cortex, with clusters in the left middle frontal gyrus and right superior frontal gyrus showing the greatest cross-model stability (uncorrected voxel-level <i>p</i> < 0.001; FDR-corrected cluster-level <i>p</i> < 0.05); additional regions, including posterior cerebellum, were more sensitive to model specification. No significant voxel-wise associations were observed for ODs, and surface-based analyses yielded no significant associations with SLDs. Boys showed higher SLD rates than girls, but voxel-wise sex × SLD interactions were not significant. These findings suggest that dimensionally measured SLDs across a population-based cohort are most consistently related to frontal control systems implicated in planning and monitoring demands during speech. The overlap with frontal regions reported in diagnosis-based stuttering studies suggests that frontal control circuitry is relevant to fluency variation in early childhood across both dimensional and categorical approaches. These findings support a complementary, dimensional approach to studying fluency variation in early childhood, while underscoring the need for longitudinal work to determine how naturally occurring disfluency relates to later developmental stuttering.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754058","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}
Kaitlin L. Ingraham Dixie, Alexa M. Tierno, Michael A. Thornton, Mahlet A. Mekonnen, Erica A. Dale, Hui Zhong, V. Reggie Edgerton, Patricia E. Phelps
{"title":"Olfactory Ensheathing Cell Transplantation Combined With Electrical Epidural Stimulation as a Long-Term Treatment for Severe Spinal Cord Injury in Female Fischer 344 Rats","authors":"Kaitlin L. Ingraham Dixie, Alexa M. Tierno, Michael A. Thornton, Mahlet A. Mekonnen, Erica A. Dale, Hui Zhong, V. Reggie Edgerton, Patricia E. Phelps","doi":"10.1111/ejn.70648","DOIUrl":"https://doi.org/10.1111/ejn.70648","url":null,"abstract":"<p>Following severe spinal cord injury (SCI), transplanted olfactory ensheathing cells (OECs) reduce inhibitory factors and promote axonal outgrowth at the lesion site to help reestablish the circuit connectivity needed for functional recovery. Another promising therapy, electrical epidural stimulation, also helps to reestablish connectivity but targets the caudal spinal cord. This study asked if the combination of OEC transplantation and administration of electrical epidural stimulation during climb training would improve recovery. Inbred Fischer 344 rats received a severe-to-complete SCI and a two-week delayed transplant of OECs, media, or fibroblasts. Rats received electrical epidural stimulation while performing a climbing task 3 times/week. To evaluate connectivity across the injury site, we injected a transsynaptic retrograde tracer GFP-pseudorabies virus into the tibialis anterior of one hindlimb and RFP-pseudorabies virus into the soleus of the other. Scores on the BBB locomotor test improved for all groups over time, but no behavioural differences were detected. Importantly, the GFP-labelled OECs and fibroblasts survived in the injury site for 5.5–6.5 months. OEC treatment greatly increased the density of serotonergic and neurofilament-positive axons in the lesion core versus controls. The percent of neurofilament-positive axons associated with myelin proteins was greater in OEC- than in media-treated rats. We also found evidence of pseudorabies virus-infected propriospinal neurons that express the transcription factor Chx10 above the injury site and some were cholinergic and dually-labelled from antagonistic muscles. These results provide evidence that OEC transplantation combined with electrical epidural stimulation may be a beneficial treatment for severe SCI.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754133","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}
Dagnew Getnet Adugna, Simon Walker, Oliver Hayman, Yibeltal Yismaw Gela, Chu Gan, Dawson J. Kidgell
{"title":"Age-Related Differences in Corticospinal Function and Muscle Strength: A Systematic Review and Meta-Analysis","authors":"Dagnew Getnet Adugna, Simon Walker, Oliver Hayman, Yibeltal Yismaw Gela, Chu Gan, Dawson J. Kidgell","doi":"10.1111/ejn.70649","DOIUrl":"10.1111/ejn.70649","url":null,"abstract":"<p>Age-related declines in neuromuscular performance are well documented; however, the cortical processes underlying these changes remain unclear. This systematic review and meta-analysis compared younger and older adults across key transcranial magnetic stimulation measures of corticospinal and intracortical function, including corticospinal excitability, cortical silent period, intracortical facilitation and intracortical inhibition. Age-related differences in maximal voluntary strength were also quantified as a secondary outcome. A comprehensive literature search identified 52 eligible studies from 1682 records. Methodological quality was evaluated using a modified Downs and Black checklist, and the certainty of evidence was assessed using the GRADE approach. A random-effects model was applied to calculate standardised mean differences (SMDs) with 95% confidence intervals (CIs). Compared to younger adults, older adults produced lower maximal isometric voluntary force (SMD = −0.76) and exhibited reduced resting motor evoked potential amplitudes (SMD = −0.55) and intracortical facilitation (SMD = −0.27). These age-related differences were not observed during active contractions. Cortical silent period duration was longer in older adults (SMD = 0.39). No age-related differences were found in short- or long-interval intracortical inhibition. These findings indicate that ageing is associated with reduced resting corticospinal and intracortical excitability, prolonged cortical silent periods and lower maximal voluntary strength. As neural and strength outcomes were analysed independently, a causal relationship cannot be established, but the parallel pattern points to central neural alterations as plausible targets for future interventions aimed at mitigating age-related neuromuscular decline.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70649","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711636","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}
Renata Batista-Brito, Christian Mayer, Mercedes Paredes, Carla G. Silva
{"title":"Decoding Brain Development and Function Through GABAergic Inhibitory Neurons","authors":"Renata Batista-Brito, Christian Mayer, Mercedes Paredes, Carla G. Silva","doi":"10.1111/ejn.70650","DOIUrl":"10.1111/ejn.70650","url":null,"abstract":"<p>Cortical interneurons are essential for the formation, maturation and functional balance of mammalian brain circuits. Originating in the ventral telencephalon, they migrate into the cortex through organized streams and diversify into multiple inhibitory subtypes. Advances in molecular biology, imaging and single-cell transcriptomics have revealed the remarkable heterogeneity in their development. Understanding their molecular and functional complexity is a gateway to understanding in full their critical roles in neural synchronization, cognitive processes, sleep regulation and their potential links to the emergence of human-specific brain functions. These findings aim to inspire future studies focused on deciphering the origins of human interneuron, the diversity of interneuron functions and their implications for understanding neurodevelopmental disorders.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724178","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}
Renée Johnston, Chadwick Boulay, Laurence Hunt, Steven W. Kennerley, Adam J. Sachs
{"title":"Distinct High-Gamma Signals in Primate Prefrontal Cortex Differentiate Cue Information, Preference Revision, and Expected Reward During Value-Based Decisions","authors":"Renée Johnston, Chadwick Boulay, Laurence Hunt, Steven W. Kennerley, Adam J. Sachs","doi":"10.1111/ejn.70641","DOIUrl":"10.1111/ejn.70641","url":null,"abstract":"<p>Understanding how prefrontal cortex (PFC) signals evolve over time to support decision-making requires characterizing both the spectral and temporal structure of neural activity. High-gamma (Hγ) power in local field potentials (LFPs) reflects local population firing, yet its role in differentiating cue-driven preference revision, reward expectation, and outcome-related signals during reward-guided decisions remains unclear. We recorded LFPs from the anterior cingulate cortex (ACC), dorsolateral PFC (DLPFC), and orbitofrontal cortex (OFC) in macaques performing a multicue reward-based decision task in which up to four sequential cues indicated the expected reward associated with competing targets. Hγ power was extracted in sliding windows aligned to key task events, and support vector machine classifiers were used to decode cue-driven preference revision, reward expectation, cue value level and position, target choice, and prediction-error contrasts. Hγ responses robustly differentiated preference-reversal from confirmation trials, with subject-specific modulation patterns across PFC subregions. Cue value level and spatial position were reliably decoded across PFC, with stronger differentiation of cue value level in OFC and cue position in DLPFC. Around movement onset, Hγ activity differentiated high versus low expected reward across PFC, with decoding accuracies reaching 85% in ACC. Hγ was also modulated by unexpected reward omission, yielding 78% decoding accuracy from a single OFC channel. These findings demonstrate that Hγ activity across PFC subregions differentiates multiple computationally defined decision variables with distinct temporal profiles and overlapping regional contributions, highlighting Hγ as a robust marker of dynamic reward-guided decision processes.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711615","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}
Luana dos Santos de Oliveira, Mariana Penteado Nucci, Carla Silva-Batista, Caroline Ribeiro de Souza, Andrea Cristina de Lima-Pardini, Fabio Augusto Barbieri, Daniel Boari Coelho
{"title":"Freezing of Gait: A Tribute to Nir Giladi","authors":"Luana dos Santos de Oliveira, Mariana Penteado Nucci, Carla Silva-Batista, Caroline Ribeiro de Souza, Andrea Cristina de Lima-Pardini, Fabio Augusto Barbieri, Daniel Boari Coelho","doi":"10.1111/ejn.70647","DOIUrl":"10.1111/ejn.70647","url":null,"abstract":"<p>Freezing of gait (FoG) is frequently triggered during gait initiation, a transition that depends on anticipatory postural adjustments (APAs). However, the neuroanatomical substrates linking brain morphometry to APA control during step initiation in FoG remain unclear. We investigated whether subcortical volumes and cortical thickness in motor–cognitive regions relate to APA features and clinical severity. Forty-four right-handed individuals with midstage PD (26 PD + FoG; 18 PD − FoG) performed step initiation. FreeSurfer-derived regional volumes and cortical thickness were extracted. Associations between morphometry and APA metrics were tested across all participants and within groups. Group differences were tested using the Mann–Whitney <i>U</i> tests, and partial Spearman correlations examined morphometry–clinical and morphometry–APA associations, controlling for UPDRS-III and daily levodopa dose. Compared with PD without FoG, the PD + FoG group showed higher UPDRS-III scores and levodopa doses, lower APA mediolateral amplitudes, and larger amygdala volumes. Across all participants, longer APA duration was associated with smaller putamen, thalamus, and dorsolateral prefrontal cortex volumes, whereas greater APA mediolateral amplitude was associated with lower frontopolar cortical thickness. In PD + FoG, freezing severity and APA features were associated with distinct morphometric patterns across the basal ganglia, thalamus, prefrontal, cingulate, SMA, and insular regions. These findings suggest that gait initiation impairment in PD reflects distributed morphometric alterations rather than a single regional substrate. APA measures may provide mechanistically relevant biomechanical markers for identifying neural systems involved in FoG.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677529","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}
Maya Wilde, Dimitra Kiakou, Eduard Bakstein, Pavel Filip, Daniel Novak
{"title":"Predictive Models for Motor Outcomes From Deep Brain Stimulation in Parkinson's Disease: A Systematic Review","authors":"Maya Wilde, Dimitra Kiakou, Eduard Bakstein, Pavel Filip, Daniel Novak","doi":"10.1111/ejn.70644","DOIUrl":"https://doi.org/10.1111/ejn.70644","url":null,"abstract":"<p>Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease, but the extent of improvement in motor symptoms varies. A tool which accurately predicts patient outcomes based on data available pre-surgery would be useful for clinical decision-making and patient expectation management. Such data includes clinical and cognitive measures, neuroimaging, kinematics, functional connectivity and genetics. In this systematic review, we assess predictive models of motor outcomes from DBS. We searched the databases Web of Science, PubMed and Scopus for primary research articles that tested predictions from models based on pre-surgical data and focused on motor outcomes from DBS for Parkinson's disease. We identified 19 studies fitting these criteria. The studies with high statistical power and generalisability use only clinical data and have limited accuracy. Studies including other types of data, such as magnetic resonance imaging, may have high accuracy but are under-powered. Predictions are mostly limited to the first year after surgery, subthalamic nucleus-targeted DBS and sum scores of motor performance. Following the results of the systematic search, we discuss candidate input and output variables and validation strategies to produce predictive models that are ready for translation to clinical practice. Ideally, models would predict scores for several motor domains, over a range of time after surgery, with confidence intervals. They should also be generalisable to clinics worldwide. To achieve this goal, models and datasets should be made publicly available to enable wider validation. These recommendations provide a framework to achieve predictive models for DBS outcomes that can be used clinically.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70644","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617299","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}
Josh Murphy, Joy Krecke, Celia Morgan, Paul H. Strutton, Kirsty Bannister, Sam W. Hughes
{"title":"Pharmacological Influences on the R2 Blink Reflex Response in Healthy Participants: A Systematic Review","authors":"Josh Murphy, Joy Krecke, Celia Morgan, Paul H. Strutton, Kirsty Bannister, Sam W. Hughes","doi":"10.1111/ejn.70646","DOIUrl":"https://doi.org/10.1111/ejn.70646","url":null,"abstract":"<p>The R2 blink reflex (BR) is a polysynaptic brainstem-mediated response that can be activated by innocuous and noxious electrocutaneous stimulation of the supraorbital nerve and has been used as a biomarker across pharmacological studies. Whilst standard patch electrodes activate both the tactile (R1) and nociceptive (R2) components of the blink reflex, concentric electrodes preferentially evoke a nociceptive-specific response (NBR) by isolating the R2 component. This preregistered systematic review (CRD420251014203) aims to assess the pharmacological modulation of nociceptive R2 responses as measured by both standard patch and concentric electrodes in healthy participants. Following PRISMA guidelines, systematic searches of PubMed, Cochrane and Ovid identified studies examining R2 responses in healthy adults receiving a pharmacological intervention. Data were extracted on study design, drug category, stimulation electrode, dosage and outcome measures. Nine studies met inclusion criteria, which included eight distinct drug classes. Limited effects on the R2 response were found for opioids, selective serotonin receptor agonists, nonsteroidal anti-inflammatory drugs and ketamine. In contrast, α2-adrenoreceptor modulators, benzodiazepines, nitrous oxide and selective adenosine A1 receptor agonists demonstrated effects. The stimulation electrode used did not affect the impact of intervention on nociceptive R2 responses where comparable studies were available. These findings indicate that nociceptive R2 components of the BR, whether evoked using standard or concentric electrodes, exhibit comparable sensitivity to pharmacological modulation. Future research should further delineate the contributions of local and descending modulatory systems to nociceptive-specific and tactile processing within trigeminofacial circuits.</p>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.70646","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616713","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}
Jhonatan Rabanal-Sanchez, Carmen Rosa Silva-Correa, Miguel Angel Burgos-Flores, Kevin Jesus Mayma-Aguirre, Jimmy Andreyvan Cainamarks-Alejandro, Jonh Maximiliano Astete-Cornejo, Jaime Rosales-Rimache
{"title":"Serum Molecular Fingerprints of Oxidative Stress Underlying Neurocognitive and Motor Dysfunction in Pesticide-Exposed Populations","authors":"Jhonatan Rabanal-Sanchez, Carmen Rosa Silva-Correa, Miguel Angel Burgos-Flores, Kevin Jesus Mayma-Aguirre, Jimmy Andreyvan Cainamarks-Alejandro, Jonh Maximiliano Astete-Cornejo, Jaime Rosales-Rimache","doi":"10.1111/ejn.70645","DOIUrl":"https://doi.org/10.1111/ejn.70645","url":null,"abstract":"<div>\u0000 \u0000 <p>We investigated the relationship between chronic pesticide exposure, oxidative stress, and neurocognitive alterations in rural populations of Celendín, Cajamarca, Peru. A total of 101 adults (18–86 years) were evaluated through neuropsychological (NEUROPSI) and neuromotor assessments, serum oxidative stress biomarkers, and Fourier-transform infrared spectroscopy (FT-IR) of serum samples. Biomarkers analyzed included superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), total glutathione, lipid peroxidation (malondialdehyde), biopyrrins (BPn), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Statistical comparisons (Mann–Whitney <i>U</i>) and multivariate analyses (PCA, PLS-DA) were performed to identify biochemical and spectral alterations. Pesticide users exhibited a significantly higher frequency of attention deficit (OR = 4.4, 95% CI = 1.2–15.9) and elevated serum 8-OHdG levels (<i>p</i> = 0.042), indicating increased oxidative DNA damage. While antioxidant enzyme activities did not differ significantly, higher malondialdehyde and BPn levels suggested enhanced lipid and bilirubin oxidation. FT-IR analysis revealed distinct spectral signatures in individuals with moderate cognitive impairment, impaired left-hand motor control, and executive dysfunction (calculation). Significant bands appeared in the 440–493 cm<sup>−1</sup> region (disulfide/polysulfide bonds), 2573 cm<sup>−1</sup> (thiols), and 3630–3840 cm<sup>−1</sup> (free hydroxyl groups), consistent with oxidative protein and glycan modifications. Additional signals between 2089 and 2255 cm<sup>−1</sup> suggested carbamylation-related isothiocyanate and cyanate groups. These findings suggest that oxidative stress is a key mechanism underlying pesticide-related neurocognitive dysfunction. Combining oxidative stress biomarkers with FT-IR provides a rapid, minimally invasive approach for identifying serum molecular fingerprints with potential applications in screening and monitoring pesticide-induced neurotoxicity.</p>\u0000 </div>","PeriodicalId":11993,"journal":{"name":"European Journal of Neuroscience","volume":"64 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616712","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}