Frontiers in Molecular Neuroscience最新文献

{"title":"Editorial: Protein post-translational modifications in the nervous system: from development to disease and ageing.","authors":"Beatriz Alvarez, Judit Symmank, Geraldine Zimmer-Bensch, Miguel Diaz-Hernandez, Patricia Franzka","doi":"10.3389/fnmol.2024.1501719","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1501719","url":null,"abstract":"<p><p>PTMs are crucial for biological processes contributing to healthy organ function. Protein post-translational modifications (PTMs), such as phosphorylation (P), acetylation (Ac), SUMOylation (SUMO), S-nitrosylation (Nitro), ubiquitination (Ub) and glycosylation (Glyco), affect a wide range of cellular and biological functions as depicted in this cartoon. Perturbations lead to severe consequences for the normal function of the brain and other organs, such as muscle. Created in BioRender. Hübner (2024) BioRender.com/j49w898.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1501719"},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568282","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: ATF3: a crucial stress-responsive gene of glia and neurons in CNS.","authors":"Ronit Heinrich, Ami Aronheim, Yung-Chih Cheng, Ido Perlman","doi":"10.3389/fnmol.2024.1484487","DOIUrl":"10.3389/fnmol.2024.1484487","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1484487"},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557713","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":"Ziconotide and psychosis: from a case report to a scoping review.","authors":"Marc Peraire, Rita Gimeno-Vergara, Jennifer Pick-Martin, Mireia Boscá, Iván Echeverria","doi":"10.3389/fnmol.2024.1412855","DOIUrl":"10.3389/fnmol.2024.1412855","url":null,"abstract":"<p><p>Ziconotide is a non-opioid analgesic that acts on N-type voltage-gated calcium channels. Despite its proven effectiveness in pain treatment, it can induce neuropsychiatric symptoms. The aim of this article is to present a case of psychosis secondary to ziconotide and to explore the variety of neuropsychiatric symptoms it produces, exploring the relationship between these symptoms and the mechanism of action of ziconotide. For this purpose, a clinical case is presented as well as a scoping review of other cases published in the scientific literature. A search on Web of Science, Pubmed and Embase databases was performed on December 11, 2023, following the criteria of the PRISMA-ScR Statement. The clinical case presented shows the variety of neuropsychiatric symptomatology that ziconotide can cause in the same patient. On the other hand, 13 papers were retrieved from the scoping review (9 case reports, 4 case series), which included 21 cases of patients treated with ziconotide who presented adverse effects ranging from psychotic symptoms to delirium. In conclusion, the variety of neuropsychiatric symptoms derived from ziconotide could be related to the blockade of N-type voltage-gated calcium channels in glutamatergic and GABAergic neurons, in turn affecting dopaminergic pathways.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1412855"},"PeriodicalIF":3.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544989","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":"Pharmacological targeting of smoothened receptor cysteine-rich domain by Budesonide promotes <i>in vitro</i> myelination.","authors":"Antonella Damiana Recchia, Alessandra Dominicis, Vincenzo Maria D'Amore, Tommaso Fabiano, Aland Ibrahim Ahmed Al Jaf, Simone Peria, Francesco Basoli, Alberto Rainer, Luciana Marinelli, Francesco Saverio Di Leva, Antonella Ragnini-Wilson","doi":"10.3389/fnmol.2024.1473960","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1473960","url":null,"abstract":"<p><strong>Background: </strong>The myelin sheath ensures efficient nerve impulse transmission along the axons. Remyelination is a spontaneous process that restores axonal insulation, promoting neuroprotection and recovery after myelin damage. There is an urgent need for new pharmacological approaches to remyelination and to improve the most effective molecules. Some glucocorticoids (GC) were identified through phenotypical screens for their promyelinating properties. These GC compounds share the ability to bind the Smoothened (Smo) receptor of the Hedgehog (Hh) pathway. Gaining a deeper insight into how they modulate Smo receptor activity could guide structure-based studies to leverage the GCs' potent promyelinating activity for a more targeted approach to remyelination.</p><p><strong>Methods: </strong>Here we focused on clarifying the mechanism of action of Budesonide, a GC known to bind the Smo cysteine-rich domain (CRD) and prevent Smo translocation to the cilium in fibroblasts. Our study employed a combination of cellular, biochemical and molecular dynamics approaches.</p><p><strong>Results: </strong>We show that treating oligodendroglial cells with Budesonide promotes myelination of synthetic axons and reduces Smo CRD conformational flexibility. This inhibits the Smo-mediated canonical signaling while activating the Liver Kinase B1 (LKB1)/ AMP-activated protein kinase (AMPK) pathway, leading to Myelin basic protein (MBP) expression.</p><p><strong>Discussion: </strong>These insights pave the way for pharmacological targeting of Smo CRD to enhance oligodendrocyte precursor cells (OPCs) differentiation and improve remyelination.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1473960"},"PeriodicalIF":3.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11518828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544988","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":"Unraveling the socio-cognitive consequences of KCC2 disruption in zebrafish: implications for neurodevelopmental disorders and therapeutic interventions.","authors":"Mohammad Naderi, Thi My Nhi Nguyen, Christopher Pompili, Raymond W M Kwong","doi":"10.3389/fnmol.2024.1483238","DOIUrl":"10.3389/fnmol.2024.1483238","url":null,"abstract":"<p><p>During postnatal brain development, maintaining a delicate balance between excitation and inhibition (E/I) is essential for the precise formation of neuronal circuits. The K+/cl- cotransporter 2 (KCC2) is instrumental in this process, and its dysregulation is implicated in various neurological disorders. This study utilized zebrafish (<i>Danio rerio</i>) to investigate the socio-cognitive consequences of KCC2 disruption. Through CRISPR-Cas9 technology, biallelic <i>kcc2a</i> knockout zebrafish larvae were generated, revealing behavioral abnormalities, including impaired social interactions and memory deficits. Molecular analyses unveiled alterations in key genes associated with the GABAergic and glutamatergic systems, potentially contributing to E/I imbalance. Additionally, KCC2 disruption influenced the expression of oxytocin and BDNF, crucial regulators of social behaviors, synaptic plasticity, and memory formation. The study also explored the therapeutic potential of KCC2 modulation using pharmaceuticals, showing the rescuing effects of CLP-290 and LIT-001 on social abnormalities. However, the selective impact of LIT-001 on social behaviors, not memory, highlights the complexity of neurobehavioral modulation. In summary, this study sheds light on the pivotal role of KCC2 in shaping socio-cognitive functions and suggests potential therapeutic avenues for KCC2-related neurological disorders.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1483238"},"PeriodicalIF":3.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521684","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":"Inactivity of Stat3 in sensory and non-sensory cells of the mature cochlea.","authors":"L Bieniussa, C Stolte, P Arampatzi, J Engert, J Völker, R Hagen, S Hackenberg, K Rak","doi":"10.3389/fnmol.2024.1455136","DOIUrl":"10.3389/fnmol.2024.1455136","url":null,"abstract":"<p><p>Signal transducer and activator of transcription 3 (Stat3) plays a role in various cellular processes such as differentiation, inflammation, cell survival and microtubule dynamics, depending on the cell type and the activated signaling pathway. Stat3 is highly expressed in the hair cells and supporting cells of the cochlea and is essential for the differentiation of mouse hair cells in the early embryonic stage. However, it is unclear how Stat3 contributes to the correct function of cells in the organ of Corti postnatally. To investigate this, an inducible Cre/loxp system was used to knock out Stat3 in either the outer hair cells or the supporting cells. The results showed that the absence of Stat3 in either the outer hair cells or the supporting cells resulted in hearing loss without altering the morphology of the organ of Corti. Molecular analysis of the outer hair cells revealed an inflammatory process with increased cytokine production and upregulation of the NF-kB pathway. However, the absence of Stat3 in the supporting cells resulted in reduced microtubule stability. In conclusion, Stat3 is a critical protein for the sensory epithelium of the cochlea and hearing and functions in a cell and function-specific manner.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1455136"},"PeriodicalIF":3.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521683","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":"Inflammation and olfactory loss are associated with at least 139 medical conditions.","authors":"Michael Leon, Emily T Troscianko, Cynthia C Woo","doi":"10.3389/fnmol.2024.1455418","DOIUrl":"10.3389/fnmol.2024.1455418","url":null,"abstract":"<p><p>Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1455418"},"PeriodicalIF":3.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498774","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":"Dynamic micro-optical coherence tomography enables structural and metabolic imaging of the mammalian cochlea.","authors":"Hinnerk Schulz-Hildebrandt, Svetolik Spasic, Fang Hou, Kuan-Chung Ting, Shelley Batts, Guillermo Tearney, Konstantina M Stankovic","doi":"10.3389/fnmol.2024.1436837","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1436837","url":null,"abstract":"<p><p>Sensorineural hearing loss (SNHL) is caused by damage to the mechanosensory hair cells and auditory neurons of the cochlea. The development of imaging tools that can directly visualize or provide functional information about a patient's cochlear cells is critical to identify the pathobiological defect and determine the cells' receptiveness to emerging SNHL treatments. However, the cochlea's small size, embedded location within dense bone, and sensitivity to perturbation have historically precluded high-resolution clinical imaging. Previously, we developed micro-optical coherence tomography (μOCT) as a platform for otologic imaging in animal models and human cochleae. Here we report on advancing μOCT technology to obtain simultaneously acquired and co-localized images of cell viability/metabolic activity through dynamic μOCT (DμOCT) imaging of intracellular motion. DμOCT obtains cross-sectional images of ATP-dependent movement of intracellular organelles and cytoskeletal polymerization by acquiring sequential μOCT images and computing intensity fluctuation frequency metrics on a pixel-wise basis. Using a customized benchtop DμOCT system, we demonstrate the detailed resolution of anatomical and metabolic features of cells within the organ of Corti, via an apical cochleostomy, in freshly-excised adult mouse cochleae. Further, we show that DμOCT is capable of capturing rapid changes in cochlear cell metabolism following an ototoxic insult to induce cell death and actin stabilization. Notably, as few as 6 frames can be used to reconstruct cochlear DμOCT images with sufficient detail to discern individual cells and their metabolic state. Taken together, these results motivate future development of a DμOCT imaging probe for cellular and metabolic diagnosis of SNHL in humans.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1436837"},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498772","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 shared biomarkers and shared pathways in insomnia and atherosclerosis using integrated bioinformatics analysis.","authors":"Qichong Yang, Juncheng Liu, Tingting Zhang, Tingting Zhu, Siyu Yao, Rongzi Wang, Wenjuan Wang, Haliminai Dilimulati, Junbo Ge, Songtao An","doi":"10.3389/fnmol.2024.1477903","DOIUrl":"https://doi.org/10.3389/fnmol.2024.1477903","url":null,"abstract":"<p><strong>Background: </strong>Insomnia (ISM) is one of the non-traditional drivers of atherosclerosis (AS) and an important risk factor for AS-related cardiovascular disease. Our study aimed to explore the shared pathways and diagnostic biomarkers of ISM-related AS using integrated bioinformatics analysis.</p><p><strong>Methods: </strong>We download the datasets from the Gene Expression Omnibus database and the GeneCards database. Weighted gene co-expression network analysis and gene differential expression analysis were applied to screen the AS-related gene set. The shared genes of ISM and AS were obtained by intersecting with ISM-related genes. Subsequently, candidate diagnostic biomarkers were identified by constructing protein-protein interaction networks and machine learning algorithms, and a nomogram was constructed. Moreover, to explore potential mechanisms, a comprehensive analysis of shared genes was carried out, including enrichment analysis, protein interactions, immune cell infiltration, and single-cell sequencing analysis.</p><p><strong>Results: </strong>We successfully screened 61 genes shared by ISM and AS, of which 3 genes (<i>IL10RA</i>, <i>CCR1</i>, and <i>SPI1</i>) were identified as diagnostic biomarkers. A nomogram with excellent predictive value was constructed (the area under curve of the model constructed by the biomarkers was 0.931, and the validation set was 0.745). In addition, the shared genes were mainly enriched in immune and inflammatory response regulation pathways. The biomarkers were associated with a variety of immune cells, especially myeloid immune cells.</p><p><strong>Conclusion: </strong>We constructed a diagnostic nomogram based on <i>IL10RA</i>, <i>CCR1</i>, and <i>SPI1</i> and explored the inflammatory-immune mechanisms, which indicated new insights for early diagnosis and treatment of ISM-related AS.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1477903"},"PeriodicalIF":3.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498773","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":"Cellular signaling pathways in the nervous system activated by various mechanical and electromagnetic stimuli.","authors":"Youngjae Ryu, Aboubacar Wague, Xuhui Liu, Brian T Feeley, Adam R Ferguson, Kazuhito Morioka","doi":"10.3389/fnmol.2024.1427070","DOIUrl":"10.3389/fnmol.2024.1427070","url":null,"abstract":"<p><p>Mechanical stimuli, such as stretch, shear stress, or compression, activate a range of biomolecular responses through cellular mechanotransduction. In the nervous system, studies on mechanical stress have highlighted key pathophysiological mechanisms underlying traumatic injury and neurodegenerative diseases. However, the biomolecular pathways triggered by mechanical stimuli in the nervous system has not been fully explored, especially compared to other body systems. This gap in knowledge may be due to the wide variety of methods and definitions used in research. Additionally, as mechanical stimulation techniques such as ultrasound and electromagnetic stimulation are increasingly utilized in psychological and neurorehabilitation treatments, it is vital to understand the underlying biological mechanisms in order to develop accurate pathophysiological models and enhance therapeutic interventions. This review aims to summarize the cellular signaling pathways activated by various mechanical and electromagnetic stimuli with a particular focus on the mammalian nervous system. Furthermore, we briefly discuss potential cellular mechanosensors involved in these processes.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1427070"},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462937","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}