Multi-omic perspectives on neuroimmune mechanisms in substance use and neurodegenerative disorders

The neuroimmune system is increasingly recognized as a key regulator of brain function and disease. Microglia, astrocytes, infiltrating immune cells, and peripheral immune signals contribute to the initiation and progression of substance use disorders (SUDs) and neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. Chronic exposure to addictive substances can alter microglial states, disrupt blood–brain barrier function, and promote persistent neuroinflammatory responses. Comparable alterations in immune signaling are also implicated in neurodegeneration, where they may influence synaptic dysfunction, neuronal vulnerability, and disease progression. Recent single-cell, single-nucleus, spatial transcriptomic, epigenomic, and proteomic studies have revealed substantial cellular and molecular heterogeneity within affected tissues. However, the regulatory mechanisms connecting immune-cell states to disease phenotypes remain incompletely defined. In particular, neuroimmune alterations in SUDs are less extensively characterized than those in neurodegenerative diseases, and the extent to which shared or disease-specific mechanisms operate across these conditions remains unclear.This Research Topic aims to advance the mechanistic understanding of neuroimmune dysfunction in SUDs and neurodegenerative diseases through the application and development of multi-omic approaches. By considering these disease contexts together, the Topic will address common questions concerning how chronic pharmacological or neurodegenerative insults reshape microglial and peripheral immune-cell states, alter gene-regulatory programs, and influence communication between the central and peripheral immune systems. It will also examine whether neuroimmune signatures are conserved across disorders or reflect disease-specific processes. Contributions may apply, benchmark, or develop experimental and computational methods capable of resolving cellular heterogeneity, regulatory interactions, spatial organization, and disease-associated molecular changes in human tissues, patient-derived samples, or relevant experimental models.To gather further insights into multi-omic approaches for defining neuroimmune mechanisms in SUDs and neurodegenerative diseases, this Research Topic will focus on studies addressing the following themes:• Single-cell and single-nucleus transcriptomic, epigenomic, and proteomic profiling of microglia, astrocytes, and infiltrating immune cells• Spatial transcriptomic and spatial proteomic analysis of neuroimmune interactions in brain tissue• Chromatin accessibility, transcription-factor activity, and gene-regulatory network analysis• Peripheral immune profiling and mechanisms of peripheral-to-central immune communication• Integrated analysis of transcriptomic, epigenomic, proteomic, and spatial datasets• Computational approaches for cell-state classification, deconvolution, trajectory inference, and regulatory-network reconstruction• Comparative analyses of shared and disease-specific neuroimmune signatures across SUDs and neurodegenerative diseases• Multi-omic biomarker discovery in clinical cohorts, patient-derived samples, or postmortem tissue• Methodological advances for reproducible, interpretable, and clinically relevant neuroimmune data integration Topic editors: Avinash Veerappa, Subhash Chand, Zuleide Maria Ignácio Source: https://www.frontiersin.org/research-topics/86056/multi-omic-perspectives-on-neuroimmune-mechanisms-in-substance-use-and-neurodegenerative-disorders