Frontiers in Molecular Neuroscience最新文献

{"title":"A Na_V1.8^FlpO mouse enabling selective intersectional targeting of low threshold C fiber mechanoreceptors and nociceptors.","authors":"John C Y Chen, Lech Kaczmarczyk, Walker S Jackson, Max Larsson","doi":"10.3389/fnmol.2025.1574219","DOIUrl":"10.3389/fnmol.2025.1574219","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1574219"},"PeriodicalIF":3.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12172507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316627","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":"Exposure to a nanoplastic-enriched diet for fourteen days increases microglial immunoreactivity in the zebrafish telencephalon.","authors":"Robert A Mans, Hannah Kelehear, Sarah Rotschafer, Clare Ganas, Brendan Uche-Moon, Gabrielle Call, Callie C Mauersberg, Justin Toller, Andrew Diamanduros","doi":"10.3389/fnmol.2025.1563086","DOIUrl":"10.3389/fnmol.2025.1563086","url":null,"abstract":"<p><p>Microscopic plastic particles (micro- and nanoplastics) are an emerging environmental contaminant detected in air, soil, water, and human food supplies. Experiments using zebrafish have shown that polystyrene nanoplastics will infiltrate numerous organ systems after ingestion, including the brain, liver, muscle, and reproductive organs. Additionally, work in rodent models and cell culture has demonstrated that nanoplastics can induce inflammatory responses by microglia and alter astrocyte function. However, the responses of microglia and astrocytes in the zebrafish brain caused by daily exposures to nanoplastics have not been tested previously. In the current study, adult zebrafish were exposed to a nanoplastic-enriched diet consisting of <i>Artemia</i> brine shrimp containing 44 nm polystyrene spheres, and reactive gliosis by microglia and astrocytes was examined. Microglial 4C4-immunoreactive protein was elevated in the brains of zebrafish exposed to the nanoplastic-enriched diet. Levels of glial fibrillary acidic protein (GFAP) were not affected by plastic exposure. It was determined that microglial, but not astrocytic, markers were elevated in the zebrafish brain after 14-days of exposure to a nanopolystyrene-enriched diet. These findings contribute to our understanding of how a pervasive environmental contaminant, nanoplastics, may impair brain health, especially during the initial stages of nanoplastic exposure. Additionally, this is the first study using zebrafish to evaluate glial activation in the context of nanoplastic-contaminated foods.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1563086"},"PeriodicalIF":3.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266047","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":"Chromatin modifiers in neurodevelopment.","authors":"Sarallah Rezazadeh, Hong Ji, Cecilia Giulivi","doi":"10.3389/fnmol.2025.1551107","DOIUrl":"10.3389/fnmol.2025.1551107","url":null,"abstract":"<p><p>Emerging sequencing studies highlight the critical role of chromatin regulatory mechanisms in human diseases, particularly in neurodevelopmental and neurological disorders. Insights gained from these studies and model organism research reveal the intricate involvement of chromatin regulators in neurodevelopment, raising compelling questions about how mutations in these ubiquitous proteins drive specific dysfunctions in the nervous system. This mini review delves into key chromatin modifiers, including the histone methyl transferases NSD1 and ASH1L, the methyl-CpG-binding repressor MeCP2, and the enzymatic repressor EZH2. While functions of these proteins are relatively well-studied, the roles of many other chromatin modifiers in neurodevelopment remain poorly understood. Existing therapies targeting chromatin modifiers have shown promise, with some achieving significant clinical success. The possibility that neurological dysfunctions may be treatable even later in life underscores the urgency of prioritizing chromatin modifiers as therapeutic targets. In this mini review, we critically evaluate the current understanding of chromatin modifiers, focusing on methylation, and spotlight their pivotal roles in early brain development and neurological disorders. By advancing this field, we aim to inspire progress toward innovative treatments for these challenging conditions.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1551107"},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225251","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":"Exploring hypoxia-related genes in spinal cord injury: a pathway to new therapeutic targets.","authors":"Shihuan Cheng, Le Li, Mengmeng Xu, Ningyi Ma, Yinhua Zheng","doi":"10.3389/fnmol.2025.1565430","DOIUrl":"10.3389/fnmol.2025.1565430","url":null,"abstract":"<p><strong>Introduction: </strong>Spinal cord injury (SCI) remains a debilitating condition with limited therapeutic options. Exploring hypoxia-related genes in SCI may reveal potential therapeutic targets and improve our understanding of its pathogenesis.</p><p><strong>Methods: </strong>We developed a diagnostic model using LASSO regression and Random Forest algorithms to investigate hypoxia-related genes in SCI. The model identified critical biomarkers by analyzing differentially expressed genes (DEGs) and hypoxia-related DEGs (HRDEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to explore the biological roles of HRDEGs. The model's accuracy was validated using receiver operating characteristic curves, calibration plots, decision curves, and qPCR experiments.</p><p><strong>Results: </strong>The diagnostic model identified Casp6, Pkm, Cxcr4, and Hexa as critical biomarkers among 186 HRDEGs out of 9,732 altered genes in SCI. These biomarkers were significantly associated with SCI pathogenesis. GO and KEGG analyses highlighted their roles in hypoxia responses, particularly through the hypoxia-inducible factor 1 pathway. The model demonstrated high accuracy, with an area under the curve exceeding 0.9. GSEA and GSVA revealed distinct pathways in low- and high-risk SCI groups, suggesting potential clinical stratification strategies.</p><p><strong>Discussion: </strong>This study constructed a diagnostic model that confirmed <i>Casp6</i>, <i>Pkm</i>, <i>Cxcr4</i>, and <i>Hexa</i> as important biomarkers for SCI. The findings provide valuable insights into SCI pathogenesis and pave the way for novel treatment strategies. The integration of multi-omics data and comprehensive bioinformatics analyses offers a robust framework for identifying therapeutic targets and improving patient outcomes.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1565430"},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215525","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":"Potential therapeutic effects of ibudilast and retinoic acid against cuprizone-induced behavioral and biochemical changes in mouse brain.","authors":"Kholoud A Alyami, Gadah A Alshahrany, Kholoud M Al-Otaibi, Mohammad Z Alam, Badrah S Alghamdi, Hadeil M Alsufiani, Nouf O Alshareef, Hanna M Alhoraibi, Sahar A Alkhodair, Ulfat M Omar","doi":"10.3389/fnmol.2025.1567226","DOIUrl":"10.3389/fnmol.2025.1567226","url":null,"abstract":"<p><p>Ibudilast (IBD) is a new drug that has been released as treatment for multiple sclerosis (MS). Retinoic acid (RA), a metabolite of vitamin A, is known for its pro-regenerative and anti-inflammatory properties, therefore, it has been suggested as a supplementary treatment for MS. The objective of this study is to investigate the therapeutic effects of RA and IBD against cuprizone (CPZ) induced mouse models. Seventy-two Swiss Albino male Mice (SWR/J) were divided into two main groups control (<i>n</i> = 18); normal chow and CPZ (<i>n</i> = 54); 0.25% of CPZ mixed into chow at demyelination stage (first 5 weeks). The following 4 weeks included two stages of remyelination: early remyelination (2 weeks after CPZ discontinuation) and late remyelination (week 9). In the early stage of remyelination, the CPZ group was divided into four subgroups beside daily treatment intraperitoneal injections CPZ (+ve control- no treatment), RA (20 mg/kg), IBD (10 mg/kg), and RA + IBD, with (<i>n</i> = 12/group), while the control group had 12 mice. At the end of each stage 6 mice/ group were sacrificed. Mice response to different treatments was assessed using several locomotor and cognitive behavior tests including open field test, rotarod test, grip strength test, novel object recognition test (NORT) and Y-maze test. The expression levels of several genes MS associated genes Tumer Necrosis Factor- Alpha (TNF- <i>α</i>), Cyclooxygenase-2 (COX-2), Nerve Growth Factor (NGF), Signal transducer and activator of transcription 3 (STAT-3) and Nuclear factor kappa-light-chain-enhancer of activated b-cell (NFKB-P105) in the brain of mice were measured using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis. The results demonstrated that RA supplementation helped in alleviating the symptoms of MS induced mice with or without using IBD treatment. This was indicated as an improvement in locomotor activity, motor coordination and muscular strength as well as improving the cognition and memory functions. The mRNA expression pattern of various MS associated genes indicated that the treatments effectively mitigated the detrimental effects of CPZ in mouse brain. The findings of this study indicate that RA supplements could be effectively unitized as adjuvant therapy alongside with IBD for MS treatment.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1567226"},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215526","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":"Editorial: Molecular mechanisms of glutamatergic synapse function and dysfunction, volume II.","authors":"Dhrubajyoti Chowdhury, Jonathan G Murphy","doi":"10.3389/fnmol.2025.1618161","DOIUrl":"https://doi.org/10.3389/fnmol.2025.1618161","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1618161"},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215524","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":"Regulatory mechanism of circular RNAs in brain and neurodegenerative diseases.","authors":"Mandana Amelimojarad, Melika Amelimojarad","doi":"10.3389/fnmol.2025.1507575","DOIUrl":"10.3389/fnmol.2025.1507575","url":null,"abstract":"<p><p>Recent advancements in sequencing technology have allowed scientists to study the function and expression of different non-coding RNAs (ncRNAs). Circular RNAs (circRNAs) are increasingly recognized as prognostic and diagnostic biomarkers. These classes of ncRNAs are closed loops that are made from alternative mRNA splicing and can be found in large quantities with their evolutionarily conserved features across different species. These circRNAs can be derived from both coding and non-coding transcript and regulate cellular proteins and the expression of linear mRNA transcripts via their ability to act as miRNA sponges at various levels. Different circRNAs can affect the neurodegenerative disease pathogenesis such as Alzheimer's disease (AD), via altering a variety of methods. However, there is still limited knowledge about circRNAs in brain cells. Therefore, in this review, we will focus on the role of circRNAs in the brain to reveal a new potential therapeutic target and open the door to novel therapies and improved management of brain and neurodegenerative diseases.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1507575"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198896","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":"Bidirectional substance P signaling between periodontal ligament fibroblasts and sensory neurons under mechanical stress.","authors":"Judit Symmank, Lara Löffler, Ulrike Schulze-Späte, Collin Jacobs","doi":"10.3389/fnmol.2025.1583908","DOIUrl":"10.3389/fnmol.2025.1583908","url":null,"abstract":"<p><strong>Introduction: </strong>Orthodontic tooth movement (OTM) and treatment-associated pain are closely related processes driven by a local inflammatory response modulated by periodontal ligament fibroblasts (PdLFs). Increased levels of substance P (SP), a well-characterized tachykinin, has been demonstrated in the PdL following the application of orthodontic forces. Although traditionally considered as neurotransmitter modulating inflammatory processes and pain, recent evidence suggests that also non-neuronal cells contribute to SP signaling during OTM. Since sensory neurons also express the corresponding receptor NK1R, activation by SP appears to be possible. However, the contribution of PdLFs to SP signaling upon mechanical stress and their subsequent interaction with sensory neurons remain largely unexplored. Thus, the aim of the study was to investigate a potential SP-mediated interactions between PdLFs and sensory neurons advancing our understanding of molecular mechanisms underlying orthodontic pain during OTM.</p><p><strong>Methods: </strong>TAC1 and SP levels were quantified via qRT-PCR, Western blot, and ELISA in compressed human PdLFs. Their conditioned medium was applied to sensory-like SH-SY5Y neurons and their activation was assessed by morphological features, cFOS expression, and calcium influx. Conversely, PdLFs were stimulated with conditioned medium from capsaicin-activated SH-SY5Y neurons. Subsequently, cytokine expression, RANKL/OPG ratio and activation of immune cells and osteoclasts by PdLFs were evaluated.</p><p><strong>Results: </strong>Compressive force induced a time- and intensity-dependent increase in TAC1 expression and SP secretion by compressed PdLFs with a peak at 24 h. Stressed PdLFs significantly increased neurite complexity, cFOS levels and calcium influx in sensory neurons, indicating their activation. Conversely, activated neurons elicited a robust pro-inflammatory response in PdLFs along with an increased osteoclastogenesis.</p><p><strong>Discussion: </strong>Our findings demonstrate that PdL fibroblasts could function as a novel non-neuronal source of SP modulating sensory neuron activation. Conversely, fibroblasts were also stimulated by SP effecting inflammation and osteoclastogenesis. These findings underscore a dynamic role of PdLF- and sensory neuron-derived SP that likely contributes to both pain perception and inflammatory bone remodeling during OTM.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1583908"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198895","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":"Changes in glycinergic neurotransmission alter mammalian retinal information processing.","authors":"Anneka Joachimsthaler, Katharina Hauf, Anja Armbruster, Shiri Zayit-Soudry, Efrat Naaman, Ido Perlman, Rina Leibu, Alina Kurolap, Hagit Baris Feldman, Jan Kremers, Volker Eulenburg","doi":"10.3389/fnmol.2025.1564870","DOIUrl":"10.3389/fnmol.2025.1564870","url":null,"abstract":"<p><p>Glycine, along with GABA, constitutes the major inhibitory neurotransmitter in the central nervous system. In the retina, glycinergic neurotransmission is primarily used by amacrine cells that are involved in the lateral processing of visual stimuli in the inner retina. We have previously shown that the high-affinity glycine transporter 1 (GlyT1), that is commonly used as a reliable marker for glycinergic amacrine cells in the retina, is essential for glycinergic neurotransmission by these cells. Abolishment of retinal GlyT1 expression results in a breakdown of glycinergic neurotransmission by AII amacrine cells, but most likely also by other glycinergic amacrine cell populations. However, the impact of loss of glycinergic neurotransmission on retinal signal processing and visually guided behavior, has not yet been elucidated. In this study, the effects of loss of retinal GlyT1 expression in glycinergic amacrine cells on the optomotor reflex and on the photopic and scotopic electroretinogram (ERG) responses were analyzed. We show that retinal GlyT1-deficient mice have normal optomotor responses to rotating black and white stripes. When stimuli with sawtooth luminance profiles were used, thereby differentially activating ON and OFF pathways, the GlyT1 deficient mice showed facilitated responses to ON preferring stimuli, whereas responses to OFF preferring stimuli were unchanged. These findings were corroborated by ERG recordings that showed undistinguishable responses after flash stimulation but revealed differences in the differential processing of ON and OFF preferring stimuli. To determine if the function of retinal GlyT1 is conserved in humans, we analyzed ERG recordings from a patient diagnosed with GlyT1 encephalopathy. We show that GlyT1 deficiency results in marked ERG changes, characterized by an almost complete loss of the \"photopic hill\" phenomenon, a hill-like appearance of the relationship between the b-wave amplitude and log light stimulus strength under background illumination conditions, and reductions in the ERG oscillatory potentials in the dark- and light-adapted states. Both findings are consistent with an altered interaction between ON- and OFF pathways in the retina. Taken together our data show that glycinergic neurotransmission in the retina has important functions in retinal ON and OFF processing both in mice and humans.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1564870"},"PeriodicalIF":3.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142336","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":"Current advances on RIPK2 and its inhibitors in pathological processes: a comprehensive review.","authors":"Shanshan Shen, Chen Lu, Tao Ling, Yanan Zheng","doi":"10.3389/fnmol.2025.1492807","DOIUrl":"10.3389/fnmol.2025.1492807","url":null,"abstract":"<p><p>Receptor-Interacting Protein Kinase 2 (RIPK2) is a critical component of the signaling pathways downstream of Nucleotide-binding oligomerization domain-like receptor (NOD-like receptor), playing a vital role in the immune response, particularly in the context of cellular transport, adaptive immunity, and tumorigenesis. Recent advances have further clarified the complex roles of RIPK2, offering insights into its structural and functional characteristics. In this review, we provide a comprehensive overview of RIPK2's involvement in signaling, examine the development of RIPK2 inhibitors, and discuss novel strategies for targeting RIPK2 in therapeutic applications. Additionally, we highlight the dynamic interactions between RIPK2 and NOD-like receptors and explore future directions for improving RIPK2-targeted therapies.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1492807"},"PeriodicalIF":3.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127242","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}