Journal of Neuroscience Methods最新文献

{"title":"Intra-Rater Reliability and Validity of Neuro-Mobinavigation: A Mobile App and Laser-Guided System of Motor HotSpot Localization.","authors":"Hussein Youssef, Ali Emre Öge, Koen Cuypers, Atay Vural","doi":"10.1016/j.jneumeth.2025.110374","DOIUrl":"https://doi.org/10.1016/j.jneumeth.2025.110374","url":null,"abstract":"<p><strong>Background: </strong>Optimal transcranial magnetic stimulation (TMS) efficacy depends on precise coil placement and orientation, as even minor deviations can significantly change the excitation evoked when stimulating the primary motor cortex (M1). To compare the intra-rater reliability of a novel method for consistent TMS coil orientation over a predetermined hotspot in M1, and to benchmark its accuracy against non-navigated method.</p><p><strong>New method: </strong>A three-step method was employed. First, a laser-guided-system stabilized head position. Second, a mobile-app monitored coil tilt and orientation. Finally, coil position was marked on participant's head cap for visual reference for both methods. Twenty-nine healthy-participants underwent six TMS blocks of 20 pulses each. Six experimental blocks, alternating between non-navigated-TMS and Neuro-Mobinavigated-TMS, to investigate the parameters of motor evoked potential (MEP). The experimental blocks were quasi-randomized with a five-minute interval.</p><p><strong>Results and comparison with existing method(s): </strong>The novel method demonstrated excellent intra-rater reliability (ICC = 0.95, 95% CI: 0.90-0.97) compared to moderate intra-rater reliability of the non-navigated TMS (ICC = 0.73, 95% CI: 0.57-0.85) for MEP peak amplitude. Repeated measures ANOVA for novel-method showed consistent peak amplitude across three blocks (p = 0.078), non-navigated TMS exhibited significant variations (p < 0.0001). Wilcoxon signed rank test revealed significantly higher mean peak amplitudes for the novel method (1.02 ± 0.74) compared to non-navigated TMS (0.78 ± 0.61) (p < 0.001), small effect size (r = 0.35).</p><p><strong>Conclusions: </strong>Neuro-Mobinavigation is superior to non-navigated method and provides a reliable and cost-effective alternative for MEP studies where gold standard neuronavigation is not available.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110374"},"PeriodicalIF":2.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074767","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":"Does intra-epidermal electrical stimulation activate mechano- and thermo-nociceptors? A discrimination approach.","authors":"S U Júlio, M Schneuwly, P S Scheuren, M Hubli, M Schubert","doi":"10.1016/j.jneumeth.2025.110382","DOIUrl":"https://doi.org/10.1016/j.jneumeth.2025.110382","url":null,"abstract":"<p><strong>Background: </strong>Objective laboratory tests are needed to diagnose lesions within the nociceptive system accurately. One approach is assessing pain-related evoked potentials (PREPs) in response to intra-epidermal electrical stimulation (IES). In this context, peripheral characterization of the specificity of nociceptor activation with IES is needed.</p><p><strong>New method: </strong>As IES directly depolarizes free nerve endings, it might allow a more comprehensive nociceptor activation than classical contact heat stimulation. Hence, this study aimed to investigate whether mechano-nociceptors are activated by IES. To test this hypothesis, a heat pain model was used to assess whether IES would show comparable pain hypersensitivity in the experimentally-induced area of secondary mechanical hyperalgesia (SMH), as known for pinprick but not for contact heat stimuli. Pain ratings and PREPs were recorded in response to 15 contact heat and pinprick stimuli as well as IES applied to the volar forearm before (PRE) and after (POST) a heat pain model inducing an area of SMH (EXP) or a control model (CTRL).</p><p><strong>Results and comparison with existing methods: </strong>All 24 participants (25.5 ± 4.7 y, 10 f/14 m) presented with SMH in POST-EXP condition. Pain ratings were significantly increased in EXP versus CTRL for IES (p = 0.016) and pinprick (p = 0.006) but not for contact heat (p = 0.683). PREP NP-amplitude between EXP and CTRL was only increased in response to pinprick (p = 0.027), but not to IES (p = 0.547) and contact heat stimuli (p = 0.070).</p><p><strong>Conclusions: </strong>Psychophysical assessments suggest mechano-nociceptor activation by IES, while PREPs do not support this assumption, indicating the predominant activation of thermo-nociceptors by IES.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"416 ","pages":"110382"},"PeriodicalIF":2.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074855","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":"Ramp protocol for non-linear cerebrovascular reactivity with transcranial doppler ultrasound.","authors":"Genevieve Hayes, Sierra Sparks, Joana Pinto, Daniel P Bulte","doi":"10.1016/j.jneumeth.2025.110381","DOIUrl":"10.1016/j.jneumeth.2025.110381","url":null,"abstract":"<p><strong>Background: </strong>Cerebrovascular reactivity (CVR) reflects the ability of cerebral blood vessels to adjust their diameter in response to vasoactive stimuli, which is crucial for maintaining brain health. Traditional CVR assessments commonly use a two-point measurement, assuming a linear relationship between cerebral blood flow (CBF) and arterial CO₂. However, this approach fails to capture non-linear characteristics, particularly the plateaus at extreme CO₂ levels.</p><p><strong>New method: </strong>This study introduces a cost-effective, ramp-based end-tidal CO₂ (PETCO₂) protocol to assess non-linear aspects of CVR. Using transcranial Doppler ultrasound, we monitored blood velocity responses to progressive increases in arterial CO₂ levels in eleven healthy adults, covering a spectrum from hypocapnia to hypercapnia.</p><p><strong>Results: </strong>All eleven participants successfully completed the protocol, with an average PETCO₂ range of 26 ± 4 mmHg and blood velocity changes from -29 % to + 50 % relative to baseline. Non-linear CVR characteristics were observed in all subjects. Sigmoid models provided significantly better fits to the CVR data than linear models, while Bayesian approaches followed expected physiological ranges more accurately than least squares regression methods.</p><p><strong>Comparison with existing methods: </strong>Unlike traditional CVR methods, this ramp protocol captures the full, non-linear CVR profile. The sigmoid modeling approach offers a more accurate representation of cerebrovascular dynamics, particularly at CO₂ extremes.</p><p><strong>Conclusions: </strong>The PETCO₂ ramp protocol with non-linear CVR modeling shows promise as an accessible and reliable tool for assessing CBF dynamics. With high completion rates, straightforward implementation, and low equipment cost, this approach holds significant potential for clinical applications in cerebrovascular health evaluation.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110381"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065635","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":"Predictive models of clinical outcome of endovascular treatment for anterior circulation stroke using machine learning.","authors":"Bogey Clement, Rouchaud Aymeric, Gentric Jean-Christophe, Beaufreton Edouard, Timsit Serge, Clarencon Frederic, Caroff Jildaz, Bourcier Romain, Zhu François, Dargazanli Cyril, Hak Jean-François, Boulouis Gregoire, Ifergan Heloise, Pop Raoul, Forestier Geraud, Lapergue Bertrand, Ognard Julien","doi":"10.1016/j.jneumeth.2025.110376","DOIUrl":"10.1016/j.jneumeth.2025.110376","url":null,"abstract":"<p><strong>Background and purpose: </strong>Mechanical Thrombectomy (MT) has recently become the standard of care for anterior circulation stroke with large vessel occlusion, but predictive factors of successful MT are still not clearly defined. To tailor treatment individually for each patient, the aim of this study was to evaluate the performances of Machine Learning to predict clinical outcome (mRS) at 3 months after MT.</p><p><strong>Material and methods: </strong>From the ETIS French prospective multicenter registry, data from patients who underwent MT for anterior circulation stroke with large vessel occlusion between January 2018 and December 2020 were extracted. Three machine learning models (Support Vector Machine, Random Forest and XGBoost) have been trained with clinical, biological and brain imaging data available in emergency conditions from the cohort of patients treated from 2018 to 2019. Models' performances to predict good outcome (3-months mRS <3) were evaluated on patients treated in 2020. Performances were evaluated with AUC, accuracy, sensitivity and specificity, then ROC curves AUC were compared with the best performing model.</p><p><strong>Results: </strong>4297 patients were included, 1737 (40 %) with good outcome and 2560 (60 %) with bad outcome were used to train models and 599 patients treated in 2020 were used to evaluate their performances. The best model was obtained with XGBoost: AUC = 0.77, accuracy = 69.3 % but no statistically significant difference existed between models.</p><p><strong>Conclusion: </strong>Our study shows satisfying performances of machine learning to predict clinical outcome after MT using data easily available at initial diagnosis and before the decision to treat.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110376"},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065583","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":"Identifying Autism Spectrum Disorder Based on Machine Learning for Multi-site fMRI.","authors":"Li Kang, Mubin Chen, Jianjun Huang, Jinyang Xu","doi":"10.1016/j.jneumeth.2025.110379","DOIUrl":"https://doi.org/10.1016/j.jneumeth.2025.110379","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by repetitive stereotypical behavior and social impairment. Early diagnosis is essential for developing a treatment plan for autism. Although multi-site data can expand the dataset to facilitate the process of data analysis, data heterogeneity between sites and the large amount of data make data analysis difficult.</p><p><strong>Method: </strong>To address these issues, this paper proposes a multi-site autism identification method based on machine learning technique. Firstly, the fMRI data from all sites are converted into a glass brain dataset and their features are extracted with LeNet5. Then, the extracted glass brain features are used to construct a partial correlation matrix at subject-level and the multi-site dataset are constructed by feature selection, which is finally classified using MLP. In order to alleviate the heterogeneity of the data and improve the accuracy of data classification, a new dataset partitioning method, Split-Merge-Split (SMS), is proposed in this paper to reduce the variability between the features extracted by the model in the training and test sets.</p><p><strong>Results: </strong>Extensive quantitative and qualitative evaluations demonstrate the proposed method enhanced the recognition accuracy on both single-site and multi-site dataset, which shows the effectiveness of this method. Specifically, in single-site classification, our method achieved its highest accuracy at the OHSU site, reaching an accuracy of 93%. In multi-site classification, our method attained an accuracy of 83.5%.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110379"},"PeriodicalIF":2.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059206","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":"A Behavioral Screening Method for Predicting PTSD-like Phenotypes: Novel Application to Female Rats.","authors":"Giulia Chiacchierini, Giulia Federica Mancini, Benedetta Di Cesare, Luca Romanelli, Maria Morena, Patrizia Campolongo","doi":"10.1016/j.jneumeth.2025.110380","DOIUrl":"https://doi.org/10.1016/j.jneumeth.2025.110380","url":null,"abstract":"<p><strong>Background: </strong>Only a small percentage of trauma-exposed subjects develop PTSD, with females being twice as likely. Most rodent models focus on males and fail to account for inter-individual variability in females.</p><p><strong>New method: </strong>We tested a behavioral PTSD model in female rats to distinguish between susceptible and resilient individuals. In Experiment 1, female rats underwent footshocks paired with social isolation, a PTSD risk factor. They were re-exposed to the conditioned context to test memory retention, and assessed in the Elevated Plus Maze (EPM) and Social Interaction (SI) tests for anxiety and social behavior.</p><p><strong>Results: </strong>Footshock-exposed rats showed fear memory retention up to 16 days, indicated by elevated freezing behavior during re-exposure. They also exhibited reduced exploration in the EPM and less SI time compared to controls. In Experiment 2, we classified rats into normal responders, susceptible, and resilient groups based on locomotor activity after trauma, correlating with memory retention and anxiety.</p><p><strong>Comparison with existing methods: </strong>Unlike existing models focused on males and lacking predictive variables before trauma, our method identifies PTSD-like susceptibility and resilience in female rats by using exploratory behavior as a predictor before trauma exposure.</p><p><strong>Conclusions: </strong>Exploratory activity in a novel environment after trauma and before extinction is a reliable predictor of PTSD-like phenotypes and differentiates between susceptible and resilient female rats.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110380"},"PeriodicalIF":2.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059199","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":"Multimodal sleep signal tensor decomposition and hidden Markov Modeling for temazepam-induced anomalies across age groups.","authors":"Parikshat Sirpal, William A Sikora, Hazem H Refai","doi":"10.1016/j.jneumeth.2025.110375","DOIUrl":"10.1016/j.jneumeth.2025.110375","url":null,"abstract":"<p><strong>Background: </strong>Recent advances in multimodal signal analysis enable the identification of subtle drug-induced anomalies in sleep that traditional methods often miss.</p><p><strong>New method: </strong>We develop and introduce the Dynamic Representation of Multimodal Activity and Markov States (DREAMS) framework, which embeds explainable artificial intelligence (XAI) techniques to model hidden state transitions during sleep using tensorized EEG, EMG, and EOG signals from 22 subjects across three age groups (18-29, 30-49, and 50-66 years). By combining Tucker decomposition with probabilistic Hidden Markov Modeling, we quantified age-specific, temazepam-induced hidden states and significant differences in transition probabilities.</p><p><strong>Results: </strong>Jensen-Shannon Divergence (JSD) was employed to assess variability in hidden state transitions, with older subjects (50-66 years) under temazepam displaying heightened transition variability and network instability as indicated by a 48.57 % increase in JSD (from 0.35 to 0.52) and reductions in network density by 12.5 % (from 0.48 to 0.42) and modularity by 21.88 % (from 0.32 to 0.25). These changes reflect temazepam's disruptive impact on sleep architecture in older adults, aligning with known age-related declines in sleep stability and pharmacological sensitivity. In contrast, younger subjects exhibited lower divergence and retained relatively stable, cyclical transition patterns. Anomaly scores further quantified deviations in state transitions, with older subjects showing increased transition uncertainty and marked deviations in REM-like to NREM state transitions.</p><p><strong>Comparison with existing methods: </strong>This XAI-driven framework provides transparent, age-specific insights into temazepam's impact on sleep dynamics, going beyond traditional methods by identifying subtle, pharmacologically induced changes in sleep stage transitions that would otherwise be missed.</p><p><strong>Conclusions: </strong>DREAMS supports the development of personalized interventions based on sleep transition variability across age groups, offering a powerful tool to understand temazepam's age-dependent effects on sleep architecture.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110375"},"PeriodicalIF":2.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059254","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":"Two-brain microstates: A novel hyperscanning-EEG method for quantifying task-driven inter-brain asymmetry.","authors":"Qianliang Li, Marius Zimmermann, Ivana Konvalinka","doi":"10.1016/j.jneumeth.2024.110355","DOIUrl":"https://doi.org/10.1016/j.jneumeth.2024.110355","url":null,"abstract":"<p><strong>Background: </strong>The neural mechanisms underlying real-time social interaction remain poorly understood. While hyperscanning has emerged as a popular method to better understand inter-brain mechanisms, inter-brain methods remain underdeveloped, and primarily focused on inter-brain synchronization (IBS).</p><p><strong>New method: </strong>We developed a novel approach employing two-brain EEG microstates, to investigate neural mechanisms during symmetric and asymmetric interactive tasks. Microstates are quasi-stable configurations of brain activity that have been proposed to represent basic building blocks for mental processing. Expanding the microstate methodology to dyads of interacting participants enables us to investigate quasi-stable moments of inter-brain synchronous and asymmetric activity.</p><p><strong>Results: </strong>Conventional microstates fitted to individuals were not related to the different interactive conditions. However, two-brain microstates were modulated in the observer-actor condition, compared to all other conditions where participants had more symmetric task demands, and the same trend was observed for the follower-leader condition. This indicates differences in resting state default-mode network activity during interactions with asymmetric tasks.</p><p><strong>Comparison with existing methods: </strong>Hyperscanning studies have primarily estimated IBS based on functional connectivity measures. However, localized connections are often hard to interpret on a larger scale when multiple connections across brains are found to be important. Two-brain microstates offer an alternative approach to evaluate neural activity from a large-scale global network perspective, by quantifying task-driven asymmetric neural states between interacting individuals.</p><p><strong>Conclusions: </strong>We present a novel method using two-brain microstates, including open-source code, which expands the current hyperscanning-EEG methodology to measure and potentially identify both synchronous and asymmetric inter-brain states during real-time social interaction.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110355"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039403","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":"Isolation, culture, and characterization of primary endothelial cells and pericytes from mouse sciatic nerve.","authors":"Yan Huang, Hai-Rong Jin, Fang-Yuan Liu, Fitri Rahma Fridayana, Minh Nhat Vo, Ji-Kan Ryu, Guo Nan Yin","doi":"10.1016/j.jneumeth.2025.110366","DOIUrl":"10.1016/j.jneumeth.2025.110366","url":null,"abstract":"<p><strong>Background: </strong>The recovery of injured peripheral nerves relies on angiogenesis, where newly formed blood vessels act as pathways guiding Schwann cells across the wound to support axon regeneration. While some research has examined this process, the specific mechanisms of angiogenesis in peripheral nerve healing remain unclear. In vitro models are vital tools to investigate these mechanisms; however, no current in vitro culture methods exist for isolating vascular cells, such as endothelial cells (ECs) and pericytes, specifically from sciatic nerves.</p><p><strong>New method: </strong>We developed a straightforward and reliable technique for isolating ECs and pericytes from injured sciatic nerves, optimized for use in in vitro studies. Cell types were characterized using specific markers and phenotypic assessments, with flow cytometry confirming cell identity and determining cell purity.</p><p><strong>Results: </strong>Our method successfully isolated high-purity ECs and pericytes from injured sciatic nerves. Immunofluorescence analysis showed that primary cultured ECs exhibited strong positive staining for CD31, while pericytes stained strongly for NG2 and PDGFRβ. Flow cytometric analysis confirmed that ECs achieved a purity of 90.22 %, and pericytes reached a purity of 92.01 %. Both cell types were capable of forming organized capillary-like structures, and in co-culture systems, pericytes effectively wrapped around ECs.</p><p><strong>Comparison with existing methods: </strong>Current isolation methods for ECs and pericytes from sciatic nerves are limited. Although techniques exist for isolating these cells from other tissues, they often rely on enzymatic digestion, which can damage cell surface proteins and reduce cell viability. Our method allows for the efficient isolation of intact ECs and pericytes from sciatic nerve tissue without such drawbacks, providing a robust platform for in vitro studies.</p><p><strong>Conclusions: </strong>This newly developed method offers an effective approach to isolate ECs and pericytes from the sciatic nerve, contributing a valuable tool for investigating the function and pathology of angiogenesis in the context of sciatic nerve injury recovery.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110366"},"PeriodicalIF":2.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029083","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":"A method for HDAC activity screening in postmortem human brain. A proof-of-concept study with antipsychotics.","authors":"Oihane Martínez-Peula, Alfredo Ramos-Miguel, Carolina Muguruza, Luis F Callado, J Javier Meana, Guadalupe Rivero","doi":"10.1016/j.jneumeth.2025.110365","DOIUrl":"10.1016/j.jneumeth.2025.110365","url":null,"abstract":"<p><strong>Background: </strong>Histone deacetylase (HDAC) density and activity are altered in different brain disorders. Antipsychotic drugs (APs) might modulate HDAC activity in brains of schizophrenia subjects.</p><p><strong>New method: </strong>HDAC activity assay amenable for enzyme kinetics and HDAC inhibitor (HDACi) screening studies in postmortem human brain samples.</p><p><strong>Results: </strong>The optimization and characterization work involved several steps. The nucleosolic subcellular fraction and total protein amount needed for an optimal HDAC activity on Boc-Lys(Ac)-AMC substrate were characterized. Signal-to-noise ratio (1.8) and Z-score values (0.82) were indicators of the assay quality. Inhibition studies with non-selective (belinostat, vorinostat, valproic acid) and selective (apicidin, MS275, romidepsin, tacedinaline and EX527) HDACis showed that the optimized assay detected class I HDAC activity. The obtained IC50 values were similar to those previously reported, proving the assay reliability. We used the optimized assay to study the effect of APs on HDAC activity. Inhibition studies with APs in postmortem human brain, together with enzyme kinetic studies in brains of rats chronically treated with APs observed no modulation of class I HDAC activity.</p><p><strong>Comparison with existing methods: </strong>This study describes the optimization of a reliable and cost efficient HDAC activity assay for its use in postmortem human brain samples. The assay does not depend on antibody specificity and it is valid for enzyme kinetic studies and for the screening of new potential class I HDACis.</p><p><strong>Conclusions: </strong>We optimized and characterized an assay to measure HDAC activity in postmortem human brain samples. We did not observe any modulatory effect of APs on HDAC activity.</p>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":" ","pages":"110365"},"PeriodicalIF":2.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006315","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}