Journal of Neurochemistry最新文献

{"title":"Brain Adenylosuccinate Is Dramatically Increased Under Global Ischemia Without Evidence for Purine Nucleotide Cycle Activation","authors":"Drew R. Seeger,&nbsp;Brennon Schofield,&nbsp;Derek Besch,&nbsp;Svetlana A. Golovko,&nbsp;Peddanna Kotha,&nbsp;Mikhail Y. Golovko","doi":"10.1111/jnc.70121","DOIUrl":"https://doi.org/10.1111/jnc.70121","url":null,"abstract":"<div>\u0000 \u0000 <p>It is well documented that adenosine and adenine nucleotides, such as ATP, ADP, and AMP, undergo significant alterations within seconds upon brain ischemia. For their accurate quantification, in situ deactivation of enzymes involved in their metabolism is required to prevent postmortem alterations. Thus, techniques such as high energy head-focused microwave irradiation (MW) or freeze-blowing are often used prior to metabolome analysis. However, alterations of another important purine nucleotide, adenylosuccinate (AdSucc), under brain ischemia have not been previously addressed. AdSucc is an intermediate in purine nucleotide de novo synthesis. Over 50 years ago, it was also proposed to have a role in brain energy metabolism through the purine nucleotide cycle (PNC) similar to that in muscle, with, to the best of our knowledge, no follow-up studies. In the present study, we applied MW and LC–MS analysis for mouse brain AdSucc quantification in situ at baseline and upon 30 s, 2 min, and 10 min of global ischemia. Our data indicate that in situ enzyme deactivation is required for brain AdSucc quantification. We report, for the first time, that brain AdSucc is dramatically increased 19-fold at 30 s ischemia and 77-fold at 2 min, from 0.007 ± 0.001 to 0.136 ± 0.026 and 0.555 ± 0.036 nmol/mg of brain wet weight (ww), respectively, without further increase at 10 min, positioning it as one of the major brain metabolites under ischemia (~0.56 mM). Quantification of PNC and tricarboxylic acid cycle (TCA) metabolites did not support the role of AdSucc induction in the activation of these pathways under ischemia. Importantly, a significant AdSucc increase up to ~0.56 mM did not affect its precursor aspartate (Asp), which remained at ~1 mM (0.923 ± 0.036 nmol/mg ww) during ischemia, indicating that AdSucc is not produced by the condensation reaction between Asp and IMP in the PNC catalyzed by adenylosuccinate synthase (ADSS). Further studies are required to elucidate the mechanisms for AdSucc increase and its role under brain ischemia.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated Low-Level Inflammatory Challenge Leads to Alterations in the TNF-CXCL10 Signalling Pathway in Mouse Cerebral Endothelial Cells In Vitro","authors":"Megan Ritson,&nbsp;Dong Xia,&nbsp;Caroline Wheeler-Jones,&nbsp;Helen B. Stolp","doi":"10.1111/jnc.70130","DOIUrl":"https://doi.org/10.1111/jnc.70130","url":null,"abstract":"<p>The mechanism by which chronic systemic inflammation contributes to cerebral endothelial dysfunction and neurological disorders is unclear, although endothelial inflammatory signalling is considered a cornerstone of this process. Here, we have performed transcriptomic analysis of published RNASeq datasets and identified consistent upregulation of the Tumour Necrosis Factor—C-X-C Motif Chemokine Ligand 10 (TNF-CXCL10) signalling pathway in mouse cerebral endothelial cells following a single inflammatory challenge. We subsequently investigated the effects of repeated low-level inflammation on the modulation of this pathway in a mouse cerebral endothelial cell line, analysing the effect on markers of endothelial cell activation and changes in cellular function, as a potential mechanism underlying the cerebrovascular response to low-level systemic inflammation. Mouse cerebral endothelial cells (bEnd.3) were exposed to hour-long treatments with phosphate buffered saline (PBS), a single low concentration of TNF (0.5 ng/mL), repeated low-concentration TNF (0.5 ng/mL, 1 h × 4 days) or a single cumulative concentration of TNF (2.0 ng/mL). RNA and protein were extracted 4 and 24 h after the final treatment for analysis of gene/protein expression using qRT-PCR and western blotting. Repeated inflammatory challenge significantly upregulated both Intercellular Adhesion Molecule 1 (ICAM1) and CXCL10 at the mRNA and protein levels. Signal transducer and activator of transcription 1 (STAT1) and phosphorylated-STAT1 (pSTAT1) protein levels were also increased at 4 and 24 h. Differentially, tumor necrosis factor receptor-associated factor 2 (TRAF2) and Interferon gamma (IFNγ) gene expression were decreased at 4 h, returning to control levels at 24 h. Functional analysis revealed significant increases in endothelial cell proliferation and apoptosis in the presence of repeated TNF exposure. CXCL10 knockdown with small interfering RNA (siRNA) reduced mean caspase 3/7 activity induced by the repeated inflammatory paradigm. These data suggest an upregulation of the TNF-CXCL10 pathway in response to low-level repetitive inflammation in mouse cerebral endothelial cells. Modulation of this pathway may represent a broad therapeutic target for neurovascular disease.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMDA-Dependent Coplasticity in VIP Interneuron-Driven Inhibitory Circuits","authors":"Jadwiga Jabłońska,&nbsp;Grzegorz Wiera,&nbsp;Jerzy W. Mozrzymas","doi":"10.1111/jnc.70117","DOIUrl":"https://doi.org/10.1111/jnc.70117","url":null,"abstract":"<div>\u0000 \u0000 <p>Inhibitory plasticity is emerging as a key regulator of excitation/inhibition (E/I) balance, a fundamental determinant of brain network dynamics. While significant progress has been made in understanding inhibitory plasticity at synapses targeting excitatory principal neurons (I → E), the mechanisms and functional implications of plasticity at interneuron-interneuron (I → I) synapses remain largely unexplored. Herein, we investigated the properties and plasticity of inhibitory inputs from vasoactive intestinal peptide (VIP) interneurons onto <i>stratum oriens</i> interneurons (<i>so</i>INs) in the hippocampal CA1 region. Using optogenetics, patch-clamp electrophysiology, and morphological reconstructions, we characterized the kinetics, short-term plasticity, and NMDA receptor-dependent long-term plasticity at VIP → <i>so</i>IN synapses in two distinct <i>so</i>IN subtypes: fast-spiking (FS) and <i>oriens-lacunosum moleculare</i> (OLM)/bistratified interneurons. Optogenetically evoked VIP → <i>so</i>IN IPSCs showed faster rise times and slower decay in FS interneurons than in OLM/bistratified cells, although both subtypes exhibited similar short-term plasticity profiles. Brief NMDA receptor activation (1 min) induced long-term depression (iLTD) at VIP → OLM/bistratified synapses but not at VIP → FS synapses, underscoring subtype-specific plasticity. However, prolonged NMDA exposure (2 min) elicited iLTD in both interneuron subtypes. Interestingly, excitatory inputs to <i>so</i>INs demonstrated NMDA-induced long-term potentiation (E → I LTP) after brief NMDA exposure but not after prolonged application. Notably, coplasticity analysis in individual <i>so</i>INs revealed asymmetric co-expression of I → I LTD and E → I LTP in OLM/bistratified interneurons. In contrast, FS interneurons exhibited a duration-dependent transition between asymmetric and symmetric coplasticity. These findings reveal a target cell-specific landscape of inhibitory I → I plasticity and its co-expression with excitatory plasticity, highlighting VIP interneurons as key modulators of the E/I balance within local hippocampal circuits.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orchestrating Neural Development Through mRNA Translation Regulation","authors":"Brandon Rodrigue,&nbsp;Mathew Sajish,&nbsp;Natalina Salmaso,&nbsp;Argel Aguilar-Valles","doi":"10.1111/jnc.70128","DOIUrl":"https://doi.org/10.1111/jnc.70128","url":null,"abstract":"<p>Neural development is a highly intricate process that relies on the precise regulation of gene expression. While a significant focus has been placed on understanding the transcriptional control of brain development, the regulation of mRNA translation plays a fundamental role in controlling gene expression. mRNA translation in subcellular compartments distant from the cell body, such as neuronal growth cones and astrocytic processes, allows for a rapid response to the local environment. Thus, the regulation of mRNA translation influences neurodevelopmental mechanisms such as cell fate decisions, neural stem cell proliferation and differentiation, and axon guidance. As such, the dysregulation of mRNA translation can have profound consequences for neural development, leading to conditions like microcephaly, cortical malformations, autism spectrum disorders, and fragile X syndrome. This review provides an overview of mRNA translation mechanisms that control prenatal brain development and identifies significant knowledge gaps. Specifically, we focus on mRNA translation regulation through signaling cascades such as the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), the integrated stress response, Fragile X Messenger Ribonucleoprotein 1 (FMRP) and eukaryotic elongation factor 2/kinase (eEF2/eEF2K), all of which are critical for mRNA translational regulation and have been previously studied regarding brain development.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis of DNA Methylation and Gene Expression Reveals Key Molecular Signatures in Spatial Memory Impairment of Sepsis-Associated Encephalopathy","authors":"Xin Liu,&nbsp;Jiazhi Jiang,&nbsp;Bofu Li,&nbsp;Shiyu Peng,&nbsp;Siyuan Wang,&nbsp;Shuzhen Ran,&nbsp;Wei Wei,&nbsp;Xiang Li,&nbsp;Mian Peng","doi":"10.1111/jnc.70120","DOIUrl":"https://doi.org/10.1111/jnc.70120","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis-associated encephalopathy (SAE) is a life-threatening neurological syndrome caused by sepsis and characterized by diffuse brain dysfunction. Previous research has indicated a role for DNA methylation in sepsis. However, its involvement in SAE remains underexplored. In this study, a sepsis model was established in adult male C57BL/6J mice through intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 5 mg/kg to explore the relationship between DNA methylation and spatial memory impairment associated with SAE. Following LPS administration, the mice exhibited impaired learning and spatial memory. RNA sequencing of hippocampal tissues from SAE mouse models revealed differential gene expression, with 797 upregulated and 510 downregulated genes in the hippocampus 24 h post-LPS administration. Both GO and KEGG analyses indicated an enrichment of inflammation-related pathways. MeDIP-seq of the hippocampus identified 1628 hyper-methylated and 2245 hypo-methylated genes, with the latter being primarily enriched in synapse-related pathways. Seventy-one genes exhibited transcription trends opposite to their 5mC levels. RT-qPCR was used to validate the mRNA expression and methylation patterns of six genes, revealing that <i>Apmap</i> exhibited reduced promoter region methylation, accompanied by increased mRNA expression, while its overexpression alleviated these deficits. These findings suggest that <i>Apmap</i> may play a protective role in spatial memory impairment in SAE. The results present promising epigenetic biomarkers for early clinical diagnosis and potential therapeutic targets in SAE.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clearance Pathways for α-Synuclein in Parkinson's Disease","authors":"Margaret S. Ho","doi":"10.1111/jnc.70124","DOIUrl":"https://doi.org/10.1111/jnc.70124","url":null,"abstract":"<p>Protein aggregation and accumulation are hallmark features of neurodegenerative diseases. In Parkinson's disease, the progressive formation and propagation of α-synuclein aggregates—found in Lewy bodies and Lewy neurites—are closely linked to widespread neuronal dysfunction, dopaminergic neuron loss, and the emergence of both motor and nonmotor symptoms, including anosmia, cognitive decline, and depression. Despite their pathological significance, the mechanisms underlying the formation, spread, and clearance of these aggregates remain incompletely understood. In this review, we examine the cellular and molecular pathways responsible for the elimination of protein aggregates in the diseased brain. We first summarize various experimental models of α-synuclein pathology, followed by a discussion of the degradation mechanisms in neurons and glial cells under pathological conditions. These findings offer new insights into cell type-specific clearance pathways and highlight potential therapeutic targets for mitigating α-synuclein–associated toxicity in Parkinson's disease.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GluN2B-Derived Small Interfering Peptide (GluN2B-Sip) Protects Against Sevoflurane-Induced Neurotoxicity in Developing Rats","authors":"Kun Zhang,&nbsp;Yafang Liu,&nbsp;Zhaoxia Liao,&nbsp;Mingfang Zhang,&nbsp;Jing Zhang,&nbsp;Yujuan Li","doi":"10.1111/jnc.70118","DOIUrl":"https://doi.org/10.1111/jnc.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>Sevoflurane is widely used in pediatric anesthesia due to its rapid induction, minimal airway irritation, and stable hemodynamics. However, concerns have been raised regarding its potential adverse effects on cognition. Recent studies suggest that GluN2B-containing NMDA receptors play a key role in the memory deficits associated with sevoflurane exposure. In this study, we investigated whether the GluN2B small interfering peptide (GluN2B-sip) could protect against neurotoxicity induced by neonatal sevoflurane exposure. Our findings show that neonatal sevoflurane exposure leads to an increase in apoptosis-related proteins, long-term memory impairment, and reduced levels of synaptic proteins in the hippocampus of adolescent rats. GluN2B-sip partially restored synapse development and cognitive function. Together, these results suggest that GluN2B-sip mitigates sevoflurane-induced neurodegeneration and cognitive impairment in developing rats, providing a potential therapeutic strategy to prevent sevoflurane neurotoxicity. The Cdk5/GluN2B and Cdk5/CRMP2 signaling pathways may play central roles in this protective effect.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium Signaling Related Genes in Migraine","authors":"Mohammad Taheri,&nbsp;Ashkan Pourtavakoli,&nbsp;Solat Eslami,&nbsp;Arezou Sayad,&nbsp;Soudeh Ghafouri-Fard","doi":"10.1111/jnc.70112","DOIUrl":"https://doi.org/10.1111/jnc.70112","url":null,"abstract":"<div>\u0000 \u0000 <p>Calcium is essential for the growth of neurons during infancy as well as transmission of signals between neurons; thus, the related signaling pathways might contribute to the pathogenesis of brain disorders. Voltage-gated calcium channels are widely expressed in the trigeminovascular system and are regarded as important contributors to some forms of familial migraines. In fact, these channels participate in the migraine initiation events. We compared the expression of genes coding for ion channels, including <i>SLC1A1</i>, <i>SLC25A12</i>, <i>ATP2B2</i>, and their associated lncRNAs, namely <i>LINC01231</i>, <i>lnc-SLC25A12</i>, and <i>lnc-MTR-1</i>, between migraineurs and healthy controls. All mentioned genes and lncRNAs, except for <i>ATP2B2</i> and <i>LINC01231</i>, were shown to be up-regulated in total migraineurs compared with controls. Moreover, the expression levels of ATP2B2 were higher in patients with aura compared with those without aura (Expression ratio (95% CI) = 5.83 (2.93–11.59), <i>p</i> &lt; 0.0001). Yet, SLC25A12 was down-regulated in patients with aura as compared with those without aura (Expression ratio (95% CI) = 0.21 (0.11–0.42), <i>p</i> = 0.004). Notably, we demonstrated high specificity and sensitivity values for some genes in the differentiation of migraineurs from healthy controls. Taken together, we demonstrated significant over-expression of a number of ion channel and transporter genes and their related lncRNAs in migraineurs and suggested these genes as potential markers for this neurological condition.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface to the Special Issue “Autism Spectrum Disorder: From Genes to Therapies”","authors":"Carlo Sala","doi":"10.1111/jnc.70123","DOIUrl":"https://doi.org/10.1111/jnc.70123","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by repetitive behaviors and deficits in social interaction and communication. While its exact etiology remains unclear, both genetic and environmental factors contribute to its development. The following preface provides a synthesis of six review articles and five original research studies published in this issue that explore various mechanisms potentially underlying ASD pathology. These publications collectively investigate a range of potential mechanisms underlying ASD pathology, including altered neural connectivity, synaptic dysfunction, immune dysregulation, and epigenetic modifications.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking Sensory Information Processing: The Essential Role of Astrocytes","authors":"Juliana M. Rosa,&nbsp;Juan Aguilar","doi":"10.1111/jnc.70113","DOIUrl":"https://doi.org/10.1111/jnc.70113","url":null,"abstract":"<p>One of the most fundamental abilities of the nervous system is to perceive, integrate, and process sensory inputs from the external environment. This physiological ability, known as sensory information processing, has been extensively studied using diverse experimental models, ranging from in vivo vertebrates and invertebrates to in vitro and computational approaches. Most of these seminal studies have primarily focused on neuronal components, providing critical insights into the principles of excitation and inhibition circuit dynamics and anatomical wiring. However, studies in the last decade have shed light on the important role of astrocytes in sensory information processing. The astrocytic effect on controlling the strength and gain of sensory neuronal responses is particularly evident in awake and freely moving animals, where their modulation has a direct influence on behavioral output, positioning them as cell targets to understand sensory processing as a whole in brain (dys)function. In this review, we draw attention to new research that casts doubt on the conventional neurocentric theories of sensory processing and highlights the growing influence of astrocytes on how sensory processing is shaped across modalities.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"169 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}