Neurochemical Research最新文献

{"title":"Jiao-Tai-Wan Improves Cognitive Impairment by Regulating Nrf2/ARE/HO-1 Signaling Pathway in APP/PS1 Mice","authors":"Xin-Chen Wang,&nbsp;Guang-Liang Wu,&nbsp;Hai-Yan Cai,&nbsp;Chen-Liang Chu,&nbsp;Yan-Lu Liu,&nbsp;Han-Cheng Li,&nbsp;Jing Zheng,&nbsp;Huangbao Chen,&nbsp;Hao Lin,&nbsp;Shi-Yong Li,&nbsp;Xin Chen","doi":"10.1007/s11064-025-04515-7","DOIUrl":"10.1007/s11064-025-04515-7","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a chronic, progressive, and destructive neurodegenerative disorder that severely affects human memory, intelligence, and behavioral abilities. Jiao Tai Wan (JTW) is a classic formula composed of two traditional Chinese medicines, coptis chinensis (CC) and cinnamon (CIN), the ratio of CC and CIN is 10:1. JTW has the effects of promoting cognitive function, and improving learning and memory function. But the specific mechanism has not been systematically studied. We conducted Morris water maze and Y-maze behavioral tests, polymerase chain reaction (PCR), assay kit and ELISA, nissl’s staining, and western blotting to verified the improvement of cognitive function of JTW on APP/PS1 mice. Through behavioral experiments, JTW can improved the learning and spatial exploration abilities of APP/PS1 mice. Nissl’s staining and PCR detection of BDNF, NGF, and SYP showed that JTW can improved neurodegenerative lesions in APP/PS1 mice. By detecting the activities of A β 1–40, A β 1–42, α - secretase, β - secretase, and γ - secretase, as well as cholinergic labeling enzymes of Ach, AchE, and ChAT activities showed that JTW improved cerebral amyloidosis and cholinergic nervous system in APP/PS1 model mice. The detection of inflammatory factors and oxidative stress indicators revealed that JTW can inhibited the activity of inflammatory factors and oxidative stress. Western Blotting was used to detect the Nrf2/ARE/HO-1 pathway, and the result showed that JTW can regulate the Nrf2/ARE/HO-1 pathway to improving cognitive function of APP/PS1 mice. JTW enhanced the activity of Nrf2, regulated the Nrf2/ARE/HO-1 pathway, increased the activity of nerve growth factors, improved the cholinergic nervous system, inhibited inflammatory factors and oxidative stress, and ameliorated cognitive dysfunction in APP/PS1 mice.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861393","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":"Progressive Blood–Brain Barrier Disruption in Sleep-Restricted Young Mice: Cellular Senescence and Neuroinflammation Crosstalk","authors":"Jessica J. Avilez-Avilez,&nbsp;Jesús Enrique García-Aviles,&nbsp;Ricardo Jair Ramírez-Carreto,&nbsp;Verónica Salas-Venegas,&nbsp;Mara A. Guzmán-Ruiz,&nbsp;Fernanda Medina-Flores,&nbsp;Mina Königsberg,&nbsp;Anahí Chavarría,&nbsp;Beatriz Gómez-González","doi":"10.1007/s11064-025-04510-y","DOIUrl":"10.1007/s11064-025-04510-y","url":null,"abstract":"<div><p>Sleep loss promotes a chronic low-grade inflammatory status with increased levels of inflammatory cytokines. Sleep loss also induces low-grade neuroinflammation characterized by glial reactivity and blood–brain barrier (BBB) dysfunction, as evidenced by BBB hyperpermeability and tight junction disassembly. Additionally, it raises molecules related to the senescence-associated secretory phenotype (SASP) in aged subjects, suggesting an increase in senescent cells. Here, we assessed the impact of sleep restriction on cellular senescence, neuroinflammation, and BBB function in the cerebral cortex and hippocampus of young male C57BL/6 mice. Sleep restriction induced a progressive increase in BBB permeability after 3, 5, and 10 days, along with a higher expression of the astroglial marker, the glial fibrillary acidic protein (GFAP), and the expression of the C3 complement component. The pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) increased in a region-dependent form. Furthermore, the progressive increase of the senescence markers β-galactosidase and p21 observed in both brain regions was accompanied by a neurotoxic astroglial response. Our data suggest that sleep restriction promotes cellular senescence in the cerebral cortex and hippocampus of young mice.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04510-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861396","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":"Comparative Molecular Dynamics Reveals How LRRK2 Inhibitors Distinguish G2019S from Wild-Type","authors":"Chuancheng Wei,&nbsp;Choon Han Heh,&nbsp;Lei Cheng Lit,&nbsp;Sek Peng Chin","doi":"10.1007/s11064-025-04520-w","DOIUrl":"10.1007/s11064-025-04520-w","url":null,"abstract":"<p>Leucine-rich repeat kinase 2 (LRRK2) has become a critical drug target in Parkinson’s disease, with mutation-selective inhibitors offering promising potential for precision medicine. However, the structural similarity between G2019S and wild-type kinases presents a significant challenge in developing selective inhibitors. Although recent advances have led to inhibitors that selectively target G2019S or wild-type kinases, the selectivity mechanism of these inhibitors remains unclear. We employed molecular dynamics simulations to investigate and explore kinase-ligand interactions and identify the underlying mechanisms of selectivity. The results suggest that ligand binding drives the conformational changes, which is a key contributing factor to selectivity, rather than the strength of the ligand binding. The ligand-induced conformational changes lead to kinase destabilisation and inactivation. Additionally, key residues, such as Tyr2018 and Asp2017, were found to play pivotal roles in the selectivity. These insights underscore the importance of incorporating conformational dynamics into the design of future LRRK2 mutant-selective inhibitors.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04520-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832028","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":"Electroacupuncture Protects Against Post-stroke Cognitive Impairment by Promoting an IL-33/ST2 Axis-Mediated Microglia M2 Polarization","authors":"Yuhan Zhang,&nbsp;Zhimin Ding,&nbsp;Yamin Wang,&nbsp;Hao Liu,&nbsp;Jing Gao,&nbsp;Huiling Wang,&nbsp;Mingli Wu,&nbsp;Xiaodong Feng,&nbsp;Xin Shen","doi":"10.1007/s11064-025-04522-8","DOIUrl":"10.1007/s11064-025-04522-8","url":null,"abstract":"<div><p>Post-stroke cognitive impairment (PSCI) is a common and debilitating complication of stroke that significantly hinders rehabilitation. Electroacupuncture (EA), which integrates traditional acupuncture with electrical stimulation, has been widely applied in clinical practice and shown remarkable efficacy in treating PSCI. However, its underlying mechanisms remain largely unexplored. The PSCI rat model was established by middle cerebral artery occlusion/reperfusion (MCAO/R). EA treatment commenced 24 h after reperfusion and was administered daily for two weeks. To investigate the role of the Interleukin-33 (IL-33)/Interleukin 1 Receptor-Like 1 (ST2) signaling pathway in EA’s therapeutic effects, the ST2 inhibitor Astegolimab (Anti-ST2) was stereotactically injected into the lateral ventricle prior to EA intervention. Neurological function was evaluated using the Zea-Longa neurological deficit score, while emotional and cognitive behaviors were assessed through the open field test (OFT) and novel object recognition (NOR) test. Cerebral infarct volume was quantified using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Protein expression in the striatum was analyzed by Western blotting and immunofluorescence staining, and structural alterations were examined using hematoxylin–eosin (HE) staining. Microglial polarization in the ischemic penumbra was evaluated via double immunofluorescence staining. Serum levels of inflammatory cytokines, including interleukin (IL)-33, IL-10, IL-4, TNF-α, IL-1β, and IL-6, were determined using enzyme-linked immunosorbent assay (ELISA). EA markedly enhanced learning and memory in stroke rats, upregulated IL-33 expression, promoted M2 microglial polarization, and preserved the integrity of brain white matter. However, blockade of the IL-33/ST2 pathway with Anti-ST2 diminished the therapeutic benefits of EA, aggravated white matter injury and cerebral infarct volume, and amplified the inflammatory response. EA facilitates microglial polarization toward the M2 phenotype via the IL-33/ST2 signaling pathway, strengthens the structural integrity of cerebral white matter, and promotes neurological recovery after ischemic stroke.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832027","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":"Histamine H3 Receptor Antagonists Influence the Directional Growth of Type II Spiral Ganglion Neurites Within the Developing Cochlea of C57BL/6 Mice","authors":"Lingyi Kong,&nbsp;Heidi Olze,&nbsp;Agnieszka J. Szczepek","doi":"10.1007/s11064-025-04521-9","DOIUrl":"10.1007/s11064-025-04521-9","url":null,"abstract":"<div><p>The histamine H3 receptor (H3R) is a crucial regulator of synaptic plasticity, neurotransmitter release, and neural signaling within the central nervous system. However, its role in the cochlea remains poorly understood, even though mast cells, a rich endogenous source of histamine, have recently been documented in the mammalian cochlea. This study examined H3R expression and localization in the postnatal day 4–5 (P4-5) C57BL/6 mouse cochlea and evaluated its functional consequences under antagonist treatment. RT-qPCR analysis showed significantly higher <i>H3R</i> mRNA levels in the modiolus compared to the organ of Corti and the lateral wall. Immunofluorescence staining confirmed H3R localization in hair cells (HCs) and spiral ganglion neurons (SGNs). Dissected cochlear explants exposed to two distinct H3R antagonists—ciproxifan and pitolisant—at concentrations of 10µM, 50µM, and 100µM, displayed different responses: ciproxifan induced dose-dependent HC loss. In contrast, pitolisant caused no loss of HC but led to stereociliary abnormalities at higher concentrations. Both antagonists disrupted type II SGN neurite projections, redirecting their normal basal-directed trajectory toward the apical region. These findings implicate H3R in maintaining cochlear structural integrity and guiding SGN neurite development during early postnatal maturation. Further investigation into H3R-mediated mechanisms may reveal new therapeutic targets for hearing preservation and repair.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04521-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832031","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":"Sex-Specific Properties of Astrocytes: From Development to Evolutionary Insights","authors":"Mariza Bortolanza,&nbsp;Davide Gobbo,&nbsp;Lipao Fang,&nbsp;Anja Scheller,&nbsp;Xianshu Bai,&nbsp;Frank Kirchhoff","doi":"10.1007/s11064-025-04512-w","DOIUrl":"10.1007/s11064-025-04512-w","url":null,"abstract":"<div><p>Exploring sex-specific differences in astrocytes has emerged as a vital area of neurobiological research. This research sheds light on how astrocytes in females and males differ in their contribution to neuronal functionality, overall brain health, and various neurological disorders. These cells play a critical role in sustaining homeostasis, providing metabolic support, facilitating neurotransmitter recycling and responding to injuries to the central nervous system. Their physiology exhibits significant variability, which is influenced by factors such as sex, developmental stage, species differences and environmental conditions. This review provides an integrated overview of these factors, addressing key themes including developmental dynamics, aging, signalling mechanisms, glial interactions, responses to pathological states and cross-species comparisons.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04512-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832035","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":"Targeting IDO1 in Huntington’s Disease: Network Pharmacology and Preclinical Evidence from Coffea arabica","authors":"Vishnu Kumar Malakar,&nbsp;Dhritiman Roy,&nbsp;Chandi C. Malakar,&nbsp;Yogesh Mahadu Khetmalis,&nbsp;Pratap Chand Mali,&nbsp;Nitesh Kumar Poddar","doi":"10.1007/s11064-025-04509-5","DOIUrl":"10.1007/s11064-025-04509-5","url":null,"abstract":"<p>Huntington’s disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary motor dysfunction and progressive cognitive impairment. This study aimed to explore the therapeutic potential of <i>Coffea arabica</i> (CA) phytoconstituents using a network pharmacology-based drug repurposing approach. CA-related Phytoconstituents were identified from public databases, while HD-related targets were retrieved from the DisGeNET database. Indoleamine 2,3-dioxygenase (IDO1) and huntingtin (HTT) were identified as two common overlapping targets using Venny 2.1. Protein–protein interaction (PPI) networks were constructed by CytoScape software. Gene ontology (GO) and KEGG pathway enrichment analysis, followed by MCODE and ClueGO software, revealed IDO1, HTT, PPAR-γ, ESR1, and CASP3 as key targets in HD pathogenesis. Among CA phytoconstituents, geraniol was selected based on its high binding affinity to IDO1 (PDB: 6V52), with a docking score of–8.01 kcal/mol compared to–4.39 kcal/mol for the reference inhibitor. Density functional theory (DFT) analysis showed a dipole moment of 2.50 Debye. Molecular dynamics simulations confirmed the stability of the IDO1–geraniol complex, with key interactions involving Ser167. In a 3-nitropropionic acid (3-NP)-induced HD animal model, geraniol (15 mg/kg) significantly improved motor function and cognitive performance, reduced lipid peroxidation and nitrite levels, and restored the activities of antioxidant enzymes (SOD, GSH, catalase). Neurotransmitter alterations (GABA, DA, glutamate, AChE) were also regulated. Histological studies revealed preservation of striatal neurons. These findings suggest that geraniol exerts neuroprotective effects in HD via modulation of IDO1 activity, oxidative stress, and neurotransmitter balance.</p><p>This study integrates network pharmacology, in silico modeling, and in vivo analysis to explore geraniol, a key metabolite of <i>Coffea arabica</i>, as a multi-target agent for Huntington’s disease (HD). Geraniol showed strong binding to IDO1, restored cognitive and motor functions, balanced oxidative stress, and preserved striatal neurons in an HD rat model. Our findings suggest geraniol as a promising therapeutic candidate through modulation of IDO1, redox balance, and neurotransmitters.</p>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832299","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":"Longitudinal Brain Structural, Neurochemical, and Behavioral Changes Following Traumatic Brain Injury in Immature Rat Brain with ALCAR Treatment","authors":"Susanna Scafidi,&nbsp;Su Xu,&nbsp;Jennifer N. Jernberg,&nbsp;Tiffany Chu,&nbsp;Gary Fiskum,&nbsp;Mary C. McKenna","doi":"10.1007/s11064-025-04494-9","DOIUrl":"10.1007/s11064-025-04494-9","url":null,"abstract":"<div><p>Pediatric survivors of traumatic brain injury (TBI) suffer from long-term neurologic disabilities, including deficits in memory and learning. Proton magnetic resonance spectroscopy (¹H-MRS) can assess alterations in brain neurochemical profile non-invasively in vivo over time. Our study aimed to evaluate (1) the longitudinal metabolic alterations in the hippocampus after TBI using in vivo ¹H-MRS and MRI in developing rat brain, and (2) test whether treatment with acetyl-L-carnitine (ALCAR) affects hippocampal metabolic profile. Using a controlled cortical impact model of TBI, we used post-natal day (PND) 21 rat pups and acquired longitudinal ¹H-MRS of the ipsilateral perilesional and contralateral hippocampi 2–4 h, 24 h, 72 h, 7 days, and 21 days post injury. Behavioral analysis was performed on post-injury days (Dpi) 3–7, 14, and 21–28. ALCAR treated rats received intraperitoneal administration (100 mg/kg) at 1 h, 4 h, 12 h, and 23 h post injury. Our results show that TBI in immature brain results in long-term structural and neurochemical alterations. TBI resulted in long–term decreased hippocampal volume and a reduction in levels of glutamate (Glu), glutamine (Gln),γ-aminobutyric acid (GABA), myo-inositol (Ins) and taurine (Tau) in the ipsilateral (injured) hippocampus up to 72 h post injury. In TBI + vehicle and TBI + ALCAR groups, N-acetyl-aspartate (NAA) remained decreased 21 days post injury. Treatment with ALCAR did not significantly change hippocampal neurochemical profile at 24 h post injury. Behavioral studies in TBI-injured rats demonstrated that sensory motor function decreased initially and recovered with time. The TBI + ALCAR group performed significantly better compared to TBI + vehicle group in both sensory motor and hippocampal dependent recognition memory. Further studies with the longer duration of ALCAR administration are necessary to adequately assess the efficacy of ALCAR following pediatric TBI.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740804","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":"Chrysophanol Attenuates Cognitive Impairment, Neuroinflammation, and Oxidative Stress by TLR4/ NFκB-Nrf2/HO-1 Signaling in Ethanol-Induced Neurodegeneration","authors":"Jehan Zeb Khan,&nbsp;Syeda Rida Zainab,&nbsp;Abdullah Alattar,&nbsp;Reem Alshaman,&nbsp;Fawad Ali Shah,&nbsp;Muhammad Khalid Tipu","doi":"10.1007/s11064-025-04486-9","DOIUrl":"10.1007/s11064-025-04486-9","url":null,"abstract":"<div><p>Ethanol-induced neurodegeneration refers to the progressive loss of structure and function of neurons caused by chronic ethanol consumption. According to the World Health Organization (WHO), over 2.3 billion people globally consume alcohol. This contributes to a significant amount of alcohol-related brain damage. This study evaluated the effect of chrysophanol in ethanol-induced neurodegeneration. Mice were administered 10 mg/kg i.p. chrysophanol, 30 min after a 2 g/kg i.p. injection of ethanol, for 11 days. Y-maze, Morris water maze (MWM), and novel object recognition (NOR) test were carried out to analyze learning and memory impairment. Analysis of antioxidant levels, histopathological examinations, measurement of COX-2 &amp; NLRP3 using ELISA, and gene expression analysis of TLR4, NFκB, IL-1β, TNF-α, Caspase-3, and Nrf-2, HO-1, and in hippocampus and cortex using RT-PCR, as well as DNA damage by comet assay, were carried out. Chrysophanol has shown a remarkable impact in reversing cognitive decline and spatial memory. It effectively boosted antioxidant levels such as GSH, GST, and CAT, while simultaneously reducing the levels of MDA and NO. The histopathological analysis also showed improvement in overall morphology and survival of neurons. Chrysophanol treatment effectively showed an increase in the expression of HO-1 and Nrf-2, with a decrease in TLR4, NFκB, IL-1β, TNF-α, and Caspase-3 expression confirmed through RT-PCR. Production of inflammatory cytokines and apoptotic gene expression was successfully reversed after chrysophanol treatment. COX-2 &amp; NLRP3 levels decreased, and an improvement in DNA damage was observed after chrysophanol treatment. In conclusion, chrysophanol demonstrated remarkable neuroprotective activity against ethanol-induced neurodegeneration.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726409","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 the Matrix: The Role of Glial Cells and Systemic Signals in Perineuronal Net Dynamics","authors":"Valentino Totaro,&nbsp;Tommaso Pizzorusso,&nbsp;Paola Tognini","doi":"10.1007/s11064-025-04506-8","DOIUrl":"10.1007/s11064-025-04506-8","url":null,"abstract":"<div><p>Perineuronal nets (PNNs) are specialized, dense extracellular matrix structures that enmesh the cell bodies and dendrites of specific neurons, most notably inhibitory interneurons. Increasing evidence indicates that PNNs serve not merely as passive scaffolds but play an active and essential role in modulating synaptic plasticity and circuit physiology. They critically influence the timing of sensory system critical periods, as well as processes underlying learning, memory, and higher cognitive functions. Furthermore, dysregulation of PNN density and architecture have been associated with conditions like autism, neurodevelopmental disorders, schizophrenia and Alzheimer’s disease. Since they are extensively involved in brain function, we discuss the multitude of regulatory factors that govern the formation, maturation, and remodeling of PNNs. In particular, we focus on both molecular and cellular brain-intrinsic mechanisms, highlighting the potential contributions of microglia and astrocyte derived factors. Additionally, we consider the influence of long-range signaling cues, including the metabolic status and peripheral hormones. Analysing this complex network of interactors, we try to highlight the role of PNNs beyond neural plasticity and brain function, in a broader whole-body physiological perspective.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 4","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726412","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}