Frontiers in Molecular Neuroscience最新文献

{"title":"Nicotinic α7 receptors on cholinergic neurons in the striatum mediate cocaine-reinforcement, but not food reward.","authors":"Michael Fritz, Priscila Batista Rosa, Daniel Wilhelms, Maarit Jaarola, Johan Ruud, David Engblom, Anna M Klawonn","doi":"10.3389/fnmol.2024.1418686","DOIUrl":"10.3389/fnmol.2024.1418686","url":null,"abstract":"<p><p>The neurotransmitter acetylcholine has since long been implicated in reward learning and drug addiction. However, the role of specific cholinergic receptor subtypes on different neuronal populations remain elusive. Here, we studied the function of nicotinic acetylcholinergic alpha 7 receptors (α7 nAChRs) in cocaine and food-enforced behaviors. We found that global deletion of α7 nAChRs in mice attenuates cocaine seeking in a Pavlovian conditioned place preference paradigm and decreases operant responding to cocaine in a runway task and in self-administration, without influencing responding to palatable food. This effect can be attributed to alpha 7 receptor signaling in the striatum, as selective deletion of striatal α7 nAChRs using a viral vector approach resulted in a similar decrease in cocaine-preference as that of global deletion. To investigate which type of striatal neurons are responsible for this effect, we selectively targeted Cholinergic (ChAT-expressing) neurons and dopamine D1-receptor (D1R) expressing neurons. Mice with conditional deletion of α7 nAChRs in ChAT-neurons (α7 nAChR-ChATCre) exhibited decreased cocaine place preference and intact place preference for food, while α7 nAChR-D1RCre mice had no changes in reward learning to neither food nor cocaine. Cocaine induction of striatal immediate early gene expression of cFos, FosB, Arc and EGR2 was blocked in α7 nAChR-ChATCre mice, demonstrating the importance of α7 nAChRs on cholinergic neurons for striatal neuronal activity changes. Collectively, our findings show that α7 nAChRs on cholinergic interneurons in the striatum are pivotal for learning processes related to cocaine, but not food reward.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1418686"},"PeriodicalIF":3.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188927","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":"Impact of modulating leptin sensitivity on the transcriptomic profile of adult-derived hypothalamic mouse neurons.","authors":"Ewa Ocłoń, Artur Gurgul, Tomasz Szmatoła, Igor Jasielczuk, Miroslaw Kucharski, Joanna Zubel-Łojek, Dorota Anna Zieba","doi":"10.3389/fnmol.2024.1518737","DOIUrl":"10.3389/fnmol.2024.1518737","url":null,"abstract":"<p><p>The modulation of leptin sensitivity in hypothalamic neurons plays a crucial role in metabolic regulation and the development of obesity. Three distinct approaches, exposure to leptin (LEPA), administration of leptin antagonist (LANTA), and treatment with palmitate (PA), were explored in this study to assess their effects on adult-derived mHypoA-2/12 neurons and the resulting transcriptomic signatures. To this end, 3' mRNA-Seq transcriptome analysis was employed, unexpectedly revealing downregulation of key genes associated with the NOD-like receptor signaling pathway (<i>Irf9</i>, <i>Mapk3</i>, <i>Stat2</i>, <i>Nfkbia</i>, <i>Ikbkg</i>, <i>Rela</i>, <i>Cxcl1</i>, and <i>Traf5</i>), the C-type lectin receptor signaling pathway (<i>Nfkb2</i>, <i>Irf9</i>, <i>Mapk3</i>, <i>Stat2</i>, <i>Nfkbia</i>, <i>Ikbkg</i>, <i>Rela</i>, and <i>Ptgs2</i>), the NF kappa B signaling pathway (<i>Nfkbia</i>, <i>Ikbkg</i>, <i>Nfkb2</i>, <i>Rela</i>, <i>Traf5</i>, <i>Cxcl1</i>, and <i>Ptgs2</i>), and the IL 17 signaling pathway (<i>Nfkbia</i>, <i>Ikbkg</i>, <i>Mapk3</i>, <i>Rela</i>, <i>Traf5</i>, <i>Cxcl1</i>, and <i>Ptgs2</i>). These findings help elucidate the molecular mechanisms through which these factors influence leptin sensitivity and provide insights into the pathways implicated in the development of leptin resistance in hypothalamic neurons. The surprising downregulation of these pathways suggests a complex interplay between leptin signaling and the cellular stress response in hypothalamic neurons. This alteration may reflect adaptive mechanisms in response to prolonged leptin or fatty acid exposure. Understanding these dynamics is essential for elucidating the role of hypothalamic inflammation in the progression of leptin resistance and associated metabolic disorders.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1518737"},"PeriodicalIF":3.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364385","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":"Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library.","authors":"Pavel Uvarov, Satoshi Fudo, Cem Karakus, Andrey Golubtsov, Federico Rotondo, Tatiana Sukhanova, Shetal Soni, Coralie Di Scala, Tommi Kajander, Claudio Rivera, Anastasia Ludwig","doi":"10.3389/fnmol.2024.1505722","DOIUrl":"10.3389/fnmol.2024.1505722","url":null,"abstract":"<p><strong>Introduction: </strong>The neuron-specific K-Cl cotransporter KCC2 maintains low intracellular chloride levels, which are crucial for fast GABAergic and glycinergic neurotransmission. KCC2 also plays a pivotal role in the development of excitatory glutamatergic neurotransmission by promoting dendritic spine maturation. The cytoplasmic C-terminal domain (KCC2-CTD) plays a critical regulatory role in the molecular mechanisms controlling the cotransporter activity through dimerization, phosphorylation, and protein interaction.</p><p><strong>Methods: </strong>To identify novel CTD regulatory motifs, we used the Mu transposon-based mutagenesis system to generate a library of KCC2 mutants with 5 amino acid insertions randomly distributed within the KCC2-CTD. We determined the insertion positions in 288 mutants by restriction analysis and selected clones with a single insertion site outside known KCC2 regulatory motifs. We analyzed the subcellular distribution of KCC2-CTD mutants in cultured cortical neurons using immunocytochemistry and selected ten mutants with ectopic expression patterns for detailed characterization.</p><p><strong>Results: </strong>A fluorescent Cl^--transport assay in HEK293 cells revealed mutants with both reduced and enhanced Cl^--extrusion activity, which overall correlated with their glycosylation patterns. Live-cell immunostaining analysis of plasma membrane expression of KCC2-CTD mutants in cultured cortical neurons corroborated the glycosylation data. Furthermore, the somatodendritic chloride gradient in neurons transfected with the KCC2-CTD mutants correlated with their Cl^--extrusion activity in HEK293 cells. Gain- and loss-of-function mutant positions were analyzed using available KCC2 cryo-EM structures.</p><p><strong>Discussion: </strong>Two groups of mutants were identified based on 3D structural analysis. The first group, located near the interface of transmembrane and cytoplasmic domains, may affect interactions with the N-terminal inhibitory peptide regulating KCC2 activity. The second group, situated on the external surface of the cytoplasmic domain, may disrupt interactions with regulatory proteins. Analyzing CTD mutations that modulate KCC2 activity enhances our understanding of its function and is essential for developing novel anti-seizure therapies.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1505722"},"PeriodicalIF":3.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065119","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":"Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases.","authors":"Yinyin Xie, Wenlin Sun, Aoya Han, Xinru Zhou, Shijie Zhang, Changchang Shen, Yi Xie, Cui Wang, Nanchang Xie","doi":"10.3389/fnmol.2024.1527013","DOIUrl":"10.3389/fnmol.2024.1527013","url":null,"abstract":"<p><p>Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria and lysosomes, independent of mitophagy and the lysosomal degradation of mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk between these cell compartments, the dynamic regulation of organelle networks, and substance exchanges. Emerging evidence suggests that abnormalities in mitochondria-lysosome contact sites (MLCSs) contribute to neurological diseases, including Parkinson's disease, Charcot-Marie-Tooth (CMT) disease, lysosomal storage diseases, and epilepsy. This article reviews recent research advances regarding the tethering processes, regulation, and function of MLCSs and their role in neurological diseases.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1527013"},"PeriodicalIF":3.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058774","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: Oxytosis/ferroptosis: unraveling the mechanisms and its multifaceted role in neurodegenerative diseases.","authors":"Nawab John Dar, David Soriano Castell, Shahnawaz Ali Bhat, Pamela Maher","doi":"10.3389/fnmol.2024.1547301","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1547301","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1547301"},"PeriodicalIF":3.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052324","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":"The current state of knowledge on the role of NKG2D ligands in multiple sclerosis and other autoimmune diseases.","authors":"Aleksandra Pogoda-Wesołowska, Nina Sługocka, Agnieszka Synowiec, Klaudia Brodaczewska, Marcin Mejer-Zahorowski, Maciej Ziękiewicz, Wojciech Szypowski, Piotr Szymański, Adam Stępień","doi":"10.3389/fnmol.2024.1493308","DOIUrl":"10.3389/fnmol.2024.1493308","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease with demyelinating inflammatory characteristics. It is the most common nontraumatic and disabling disease affecting young adults. The incidence and prevalence of MS have been increasing. However, its exact cause remains unclear. The main tests used to support the diagnosis are magnetic resonance imaging (MRI) examination and cerebrospinal fluid (CSF) analysis. Nonetheless, to date, no sensitive or specific marker has been identified for the detection of the disease at its initial stage. In recent years, researchers have focused on the fact that the number of natural killer cell group 2 member D (NKG2D) family of C-type lectin-like receptor + (NKG2D+) T cells in the peripheral blood, CSF, and brain tissue has been shown to be higher in patients with MS than in controls. The activating receptor belonging to the NKG2D is stimulated by specific ligands: in humans these are major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA) and MHC class I polypeptide-related sequence B (MICB) proteins and UL16 binding 1-6 proteins (ULBP1-6). Under physiological conditions, the aforementioned ligands are expressed at low or undetectable levels but can be induced in response to stress factors. NKG2D ligands (NKG2DLs) are involved in epigenetic regulation of their expression. To date, studies in cell cultures, animal models, and brain tissues have revealed elevated expression of MICA/B, ULPB4, and its mouse homolog murine UL16 binding protein-like transcript (MULT1), in oligodendrocytes and astrocytes from patients with MS. Furthermore, soluble forms of NKG2DLs were elevated in the plasma and CSF of patients with MS compared to controls. In this review, we aim to describe the role of NKG2D and NKG2DLs, and their interactions in the pathogenesis of MS, as well as in other autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and celiac disease (CeD). We also assess the potential of these proteins as diagnostic markers and consider future perspectives for targeting NKG2D ligands and their pathways as therapeutic targets in MS.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1493308"},"PeriodicalIF":3.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046374","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":"Neurotherapeutic impact of vanillic acid and ibudilast on the cuprizone model of multiple sclerosis.","authors":"Rasha M Alderbi, Mohammad Z Alam, Badrah S Alghamdi, Hadeil M Alsufiani, Gamal S Abd El-Aziz, Ulfat M Omar, Maryam A Al-Ghamdi","doi":"10.3389/fnmol.2024.1503396","DOIUrl":"10.3389/fnmol.2024.1503396","url":null,"abstract":"<p><p>Multiple sclerosis (MS) affects 2.8 million people worldwide. Although the cause is unknown, various risk factors might be involved. MS involves the immune system attacking the central nervous system's myelin sheath, leading to neuron damage. This study used a cuprizone (CPZ)-intoxicated mouse model to simulate MS's demyelination/remyelination process. It evaluated the molecular, histological, and behavioral effects of vanillic acid (VA), a natural phenolic acid, alone and with Ibudilast (IBD), a clinically tested MS medication. Mice were divided into a control group (regular chow) and a CPZ group (0.3% cuprizone chow for 5 consecutive weeks). During remyelination, the CPZ group was split into four groups: no therapy, 10 mg/kg of IBD, 30 mg/kg of VA, and combined, each treated for 4 weeks. Behavioral, biochemical, molecular, and histopathological tests occurred in the 5^th week (demyelination), 7^th (early remyelination), and 9^th (late remyelination). Cognitive assessments were at weeks 5 and 9. VA enhanced motor, coordination, and cognitive impairments in CPZ-intoxicated mice and improved histopathological, molecular, and biochemical features during early remyelination. IBD improved behavioral abnormalities across all tests, but combined therapy showed no significant difference from single therapies. Further investigations are necessary to understand VA's mechanisms and potential as an MS treatment.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1503396"},"PeriodicalIF":3.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046359","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":"Serum metabolomic signatures of patients with rare neurogenetic diseases: an insight into potential biomarkers and treatment targets.","authors":"Nalaka Wijekoon, Lakmal Gonawala, Pyara Ratnayake, Darshana Sirisena, Harsha Gunasekara, Athula Dissanayake, Dhammika Amaratunga, Harry W M Steinbusch, Yetrib Hathout, Eric P Hoffman, Ashwin Dalal, Chandra Mohan, K Ranil D de Silva","doi":"10.3389/fnmol.2024.1482999","DOIUrl":"10.3389/fnmol.2024.1482999","url":null,"abstract":"<p><strong>Introduction: </strong>To further advance our understanding of Muscular Dystrophies (MDs) and Spinocerebellar Ataxias (SCAs), it is necessary to identify the biological patterns associated with disease pathology. Although progress has been made in the fields of genetics and transcriptomics, there is a need for proteomics and metabolomics studies. The present study aimed to be the first to document serum metabolic signatures of MDs (DMD, BMD, and LGMD 2A) SCAs (SCA 1-3), from a South Asian perspective.</p><p><strong>Methods: </strong>A total of 28 patients (SCA 1-10, SCA 2-2, SCA 3-2, DMD-10, BMD-2, LGMD-2) and eight controls (aged 8-65 years) were included. Metabolomic analysis was performed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS), with support from the Houston Omics Collaborative.</p><p><strong>Results and discussion: </strong>Amino acid metabolism was the primary altered super pathway in DMD followed by carbohydrate metabolism and lipid metabolism. In contrast, BMD and LGMD 2A exhibited a more prominent alteration in lipid metabolism followed by amino acid metabolism. In SCAs, primarily lipid, amino acid, peptide, nucleotide, and xenobiotics pathways are affected. Our findings offer new insights into the variance of metabolite levels in MD and SCA, with substantial implications for pathology, drug development, therapeutic targets and clinical management. Intriguingly, this study identified two novel metabolites associated with SCA. This pilot cross-sectional study warrants further research involving larger groups of participants, to validate our findings.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1482999"},"PeriodicalIF":3.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046361","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":"Insight into interplay between PANoptosis and autophagy: novel therapeutics in ischemic stroke.","authors":"He-Yan Tian, Yun-Xing Lei, Jing-Tao Zhou, Long-Jun Liu, Tong Yang, Yue Zhou, Jin-Wen Ge, Chen Xu, Zhi-Gang Mei","doi":"10.3389/fnmol.2024.1482015","DOIUrl":"10.3389/fnmol.2024.1482015","url":null,"abstract":"<p><p>PANoptosis is a novelly defined mode of programmed cell death that involves the activation of multiple cellular death pathways, including pyroptosis, apoptosis, and necroptosis, triggering robust inflammatory reactions. Autophagy is a crucial cellular process that maintains cellular homeostasis and protects cells from various stresses. PANoptosis and autophagy, both vital players in the intricate pathological progression of ischemic stroke (IS), a brain ailment governed by intricate cell death cascades, have garnered attention in recent years for their potential interplay. While mounting evidence hints at a crosstalk between these two processes in IS, the underlying mechanisms remain elusive. Therefore, this review delves into and dissects the intricate mechanisms that underpin the intersection of PANoptosis and autophagy in this devastating condition. In conclusion, the crosstalk between PANoptosis and autophagy in IS presents a promising target for the development of novel stroke therapies. Understanding the interplay between these two pathways offers a much-needed insight into the underlying mechanisms of IS and opens the possibility for new therapeutic strategies.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1482015"},"PeriodicalIF":3.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023181","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":"Urine miRNA signature as potential non-invasive diagnostic biomarker for Hirschsprung's disease.","authors":"Abhijit Sreepada, Rasul Khasanov, Enas Zoheer Elkrewi, Carolina de la Torre, Judith Felcht, Ahmad A Al Abdulqader, Richard Martel, Nicolás Andrés Hoyos-Celis, Michael Boettcher, Lucas M Wessel, Karl-Herbert Schäfer, María Ángeles Tapia-Laliena","doi":"10.3389/fnmol.2024.1504424","DOIUrl":"10.3389/fnmol.2024.1504424","url":null,"abstract":"<p><p>Hirschsprung's disease (HSCR) is characterized by congenital absence of ganglion cells in the gastrointestinal tract, which leads to impaired defecation, constipation and intestinal obstruction. The current diagnosis of HSCR is based on Rectal Suction Biopsies (RSBs), which could be complex in newborns. Occasionally, there is a delay in diagnosis that can increase the risk of clinical complications. Consequently, there is room for new non-invasive diagnostic methods that are objective, more logistically feasible and also deliver a far earlier base for a potential surgical intervention. In recent years, microRNA (miRNA) has come into the focus as a relevant early marker that could provide more insights into the etiology and progression of diseases. Therefore, in the search of a non-invasive HSCR biomarker, we analyzed miRNA expression in urine samples of HSCR patients. Results from 5 HSCR patients using microarrays, revealed hsa-miR-378 h, hsa-miR-210-5p, hsa-miR-6876-3p, hsa-miR-634 and hsa-miR-6883-3p as the most upregulated miRNAs; while hsa-miR-4443, hsa-miR-22-3p, hsa-miR-4732-5p, hsa-miR-3187-5p, and hsa-miR-371b-5p where the most downregulated miRNAs. Further search in miRNAwalk and miRDB databases showed that certainly most of these dysregulated miRNAs identified target HSCR associated genes, such as <i>RET, GDNF, BDNF, EDN3, EDNRB, ERBB, NRG1, SOX10;</i> and other genes implied in neuronal migration and neurogenesis. Finally, we could also validate some of these miRNA changes in HSCR urine by RT-qPCR. Altogether, our analyzed HSCR cohort presents a dysregulated miRNA expression presents that can be detected in urine. Our findings open the possibility of using specific urine miRNA signatures as non-invasive HSCR diagnosis method in the future.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1504424"},"PeriodicalIF":3.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052325","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}