Cariaga-Martínez, ArielGutierrez, Kilian JesúsRegidor, IgnacioDel Álamo, MartaSaiz-Ruiz, JerónimoAlelú-Paz, Raúl2025-12-192025-12-192025-06Cariaga-Martínez, A, Gutierrez, K J, Regidor, I, Del Álamo, M, Saiz-Ruiz, J & Alelú-Paz, R 2025, 'A Refined Approach to Isolate Interneurons for High-Validity Epigenetic Studies in Human Brain Tissue', Methods and Protocols, vol. 8, no. 3, 61. https://doi.org/10.3390/mps80300612409-9279PubMedCentral: PMC12196513unpaywall: 10.3390/mps8030061https://hdl.handle.net/10641/6840Publisher Copyright: © 2025 by the authors.Epigenetic research has made notable progress in recent years, yet our ability to explore the human brain at a cellular level remains limited. One of the main obstacles has been the difficulty of isolating specific neuronal populations from postmortem tissue—particularly interneurons, which play a central role in many psychiatric disorders. In this study, we present a practical and reproducible protocol for isolating GAD-positive interneurons from human brain samples. We isolate permeabilized cell-like structures suitable for downstream epigenetic analysis. To ensure specificity, we validated the isolated cells by comparing them with interneurons derived from human iPSCs. This approach allows for high-quality DNA extraction suitable for downstream epigenetic analysis, including methylation-specific PCR. By targeting a well-defined neuronal subtype, our method provides a solid foundation for studying the molecular changes associated with disorders such as schizophrenia and autism. This protocol opens new doors for cell-specific investigations in brain tissue, a step forward in understanding how epigenetic mechanisms contribute to neuropsychiatric pathophysiology.5242079enghttp://creativecommons.org/licenses/by-nc-nd/4.0/brain epigeneticscortical interneuronshuman brain tissueneuronal isolationBiotechnologyStructural BiologyBiochemistry, Genetics and Molecular Biology (miscellaneous)Journal ArticleYesyesjournal articleopen access10.3390/mps8030061https://www.scopus.com/pages/publications/105009290947https://www.scopus.com/pages/publications/105009290947#tab=citedBy