Molecular and Cellular Neuroscience最新文献

{"title":"Erratum to “wild type and P301L mutant Tau promote neuro-inflammation and α-Synuclein accumulation in lentiviral gene delivery models” [Mol. Cell. Neurosci. 49 (1) (2012), 44–53]","authors":"Preeti J. Khandelwal , Sonya B. Dumanis , Alexander M. Herman , G. William Rebeck , Charbel E.-H. Moussa","doi":"10.1016/j.mcn.2023.103844","DOIUrl":"10.1016/j.mcn.2023.103844","url":null,"abstract":"","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103844"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9557634","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":"Astrocyte-associated fibronectin promotes the proinflammatory phenotype of astrocytes through β1 integrin activation","authors":"Pao-Hsien Chu ,&nbsp;Shao-Chi Chen ,&nbsp;Hsin-Yung Chen ,&nbsp;Cheng-Bei Wu ,&nbsp;Wei-Ting Huang ,&nbsp;Hou-Yu Chiang","doi":"10.1016/j.mcn.2023.103848","DOIUrl":"10.1016/j.mcn.2023.103848","url":null,"abstract":"<div><p><span>Astrocytes are key players in neuroinflammation. In response to central nervous system<span><span> (CNS) injury or disease, astrocytes undergo reactive astrogliosis<span>, which is characterized by increased proliferation, migration, and glial fibrillary acidic protein<span> (GFAP) expression. Activation of the transcription factor nuclear factor-κB (NF-κB) and upregulation of downstream proinflammatory mediators in reactive astrocytes induce a proinflammatory phenotype in astrocytes, thereby exacerbating neuroinflammation by establishing an inflammatory loop. In this study, we hypothesized that excessive fibronectin<span> (FN) derived from reactive astrocytes would induce this proinflammatory phenotype in astrocytes in an autocrine manner. We exogenously treated astrocytes with monomer FN, which can be incorporated into the </span></span></span></span>extracellular matrix<span> (ECM), to mimic plasma FN extravasated through a compromised blood–brain barrier in neuroinflammation. We also induced de novo synthesis and accumulation of astrocyte-derived FN through tumor necrosis factor-α (TNF-α) stimulation. The excessive FN deposition resulting from both treatments initiated reactive astrogliosis and triggered NF-κB signaling in the cultured astrocytes. In addition, inhibition of FN accumulation in the ECM by the FN inhibitor pUR4 strongly attenuated the FN- and TNF-α-induced GFAP expression, NF-κB activation, and proinflammatory mediator production of astrocytes by interrupting FN–β1 integrin coupling and thus the inflammatory loop. In an in vivo experiment, </span></span></span>intrathecal injection of pUR4 considerably ameliorated FN deposition, GFAP expression, and NF-κB activation in inflamed spinal cord, suggesting the therapeutic potential of pUR4 for attenuating neuroinflammation and promoting neuronal function restoration.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103848"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9567559","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":"Circular RNA regulation and function in drug seeking phenotypes","authors":"Stephanie E. Sillivan,&nbsp;Aria Gillespie","doi":"10.1016/j.mcn.2023.103841","DOIUrl":"10.1016/j.mcn.2023.103841","url":null,"abstract":"<div><p><span><span>Drug overdoses have increased dramatically in the United States over the last decade where they are now the leading cause of accidental death. To develop efficient therapeutic options for decreasing drug consumption and overdose risk, it is critical to understand the neurobiological changes induced by drug exposure. Chronic systemic exposure to all drug classes, including opioids, </span>psychostimulants<span>, nicotine, cannabis, and alcohol, induces profound molecular neuroadaptations within the central nervous system that may reveal crucial information about the lasting effects that these substances impart on brain cells. </span></span>Transcriptome<span><span><span><span><span> analyses of messenger RNAs (mRNAs) have identified gene patterns in the brain that result from exposure to various classes of drugs. However, mRNAs represent only a small fraction of the RNA within the cell, and drug exposure also impacts other classes of RNA that are largely understudied, especially </span>circular RNAs. Circular RNAs (circRNAs) are a naturally occurring RNA species formed from back-splicing events during </span>mRNA processing<span> and are enriched in the nervous system. circRNAs are a pleiotropic class of RNAs and have a diverse impact on cellular function, with putative functions including regulation of </span></span>mRNA transcription, </span>protein translation<span><span><span>, microRNA sponging, and sequestration of RNA-binding proteins. Recent studies have demonstrated that circRNAs can modulate cognition and are regulated in the brain in response to drug exposure, yet very few studies have explored the contribution of circRNAs to drug seeking phenotypes. In this review, we will provide an overview of the mechanisms of circRNA function in the cell to highlight how drug-induced circRNA dysregulation may impact the molecular substrates that mediate </span>drug seeking behavior and the current studies that have reported drug-induced dysregulation of circRNAs in the brain. Furthermore, we will discuss how principles of circRNA biology can be adapted to study circRNAs in models of drug exposure and seek to provide further insight into the </span>neurobiology of addiction.</span></span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103841"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597184","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":"Computational insights into mRNA and protein dynamics underlying synaptic plasticity rules","authors":"Surbhit Wagle ,&nbsp;Nataliya Kraynyukova ,&nbsp;Anne-Sophie Hafner ,&nbsp;Tatjana Tchumatchenko","doi":"10.1016/j.mcn.2023.103846","DOIUrl":"10.1016/j.mcn.2023.103846","url":null,"abstract":"<div><p>Recent advances in experimental techniques provide an unprecedented peek into the intricate molecular dynamics inside synapses and dendrites. The experimental insights into the molecular turnover revealed that such processes as diffusion, active transport, spine uptake, and local protein synthesis could dynamically modulate the copy numbers of plasticity-related molecules in synapses. Subsequently, theoretical models were designed to understand the interaction of these processes better and to explain how local synaptic plasticity cues can up or down-regulate the molecular copy numbers across synapses. In this review, we discuss the recent advances in experimental techniques and computational models to highlight how these complementary approaches can provide insight into molecular cross-talk across synapses, ultimately allowing us to develop biologically-inspired neural network models to understand brain function.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103846"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021252","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 transcriptional response to acute cocaine is inverted in male mice with a history of cocaine self-administration and withdrawal throughout the mesocorticolimbic system","authors":"Soren D. Emerson ,&nbsp;Maxime Chevée ,&nbsp;Philipp Mews ,&nbsp;Erin S. Calipari","doi":"10.1016/j.mcn.2023.103823","DOIUrl":"10.1016/j.mcn.2023.103823","url":null,"abstract":"<div><p>A large body of work has demonstrated that cocaine-induced changes in transcriptional regulation play a central role in the onset and maintenance of cocaine use disorder. An underappreciated aspect of this area of research, however, is that the pharmacodynamic<span> properties of cocaine can change depending on an organism's previous drug-exposure history. In this study, we utilized RNA sequencing<span> to characterize how the transcriptome-wide effects of acute cocaine exposure were altered by a history of cocaine self-administration and long-term withdrawal (30 days) in the ventral tegmental area<span> (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC) in male mice. First, we found that the gene expression patterns induced by a single cocaine injection (10 mg/kg) were discordant between cocaine-naïve mice and mice in withdrawal from cocaine self-administration. Specifically, the same genes that were upregulated by acute cocaine in cocaine-naïve mice were downregulated by the same dose of cocaine in mice undergoing long-term withdrawal; the same pattern of opposite regulation was observed for the genes downregulated by initial acute cocaine exposure. When we analyzed this dataset further, we found that the gene expression patterns that were induced by long-term withdrawal from cocaine self-administration showed a high degree of overlap with the gene expression patterns of acute cocaine exposure - even though animals had not consumed cocaine in 30 days. Interestingly, cocaine re-exposure at this withdrawal time point reversed this expression pattern. Finally, we found that this pattern was similar across the VTA, PFC, NAc, and within each brain region the same genes were induced by acute cocaine, re-induced during long-term withdrawal, and reversed by cocaine re-exposure. Together, we identified a longitudinal pattern of gene regulation that is conserved across the VTA, PFC, and NAc, and characterized the genes constituting this pattern in each brain region.</span></span></span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103823"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597172","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":"Transcriptional and epigenetic regulation of microglia in substance use disorders","authors":"Samara J. Vilca ,&nbsp;Alexander V. Margetts ,&nbsp;Tate A. Pollock ,&nbsp;Luis M. Tuesta","doi":"10.1016/j.mcn.2023.103838","DOIUrl":"10.1016/j.mcn.2023.103838","url":null,"abstract":"<div><p><span><span>Microglia are widely known for their role in </span>immune surveillance<span> and for their ability to refine neurocircuitry during development, but a growing body of evidence suggests that microglia may also play a complementary role to neurons in regulating the behavioral aspects of substance use disorders. While many of these efforts have focused on changes in microglial gene expression associated with drug-taking, epigenetic regulation of these changes has yet to be fully understood. This review provides recent evidence supporting the role of microglia in various aspects of substance use disorder, with particular focus on changes to the microglial </span></span>transcriptome<span> and the potential epigenetic mechanisms driving these changes. Further, this review discusses the latest technical advances in low-input chromatin profiling and highlights the current challenges for studying these novel molecular mechanisms in microglia.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103838"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9595210","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":"Distinct subpopulations of D1 medium spiny neurons exhibit unique transcriptional responsiveness to cocaine","authors":"Robert A. Phillips III ,&nbsp;Jennifer J. Tuscher ,&nbsp;N. Dalton Fitzgerald ,&nbsp;Ethan Wan ,&nbsp;Morgan E. Zipperly ,&nbsp;Corey G. Duke ,&nbsp;Lara Ianov ,&nbsp;Jeremy J. Day","doi":"10.1016/j.mcn.2023.103849","DOIUrl":"10.1016/j.mcn.2023.103849","url":null,"abstract":"<div><p>Drugs of abuse increase extracellular concentrations of dopamine in the nucleus accumbens (NAc), resulting in transcriptional alterations that drive long-lasting cellular and behavioral adaptations. While decades of research have focused on the transcriptional mechanisms by which drugs of abuse influence neuronal physiology and function, few studies have comprehensively defined NAc cell type heterogeneity in transcriptional responses to drugs of abuse. Here, we used single nucleus RNA-seq (snRNA-seq) to characterize the transcriptome of over 39,000 NAc cells from male and female adult Sprague-Dawley rats following acute or repeated cocaine experience. This dataset identified 16 transcriptionally distinct cell populations, including two populations of medium spiny neurons (MSNs) that express the <em>Drd1</em> dopamine receptor (D1-MSNs). Critically, while both populations expressed classic marker genes of D1-MSNs, only one population exhibited a robust transcriptional response to cocaine. Validation of population-selective transcripts using RNA <em>in situ</em> hybridization revealed distinct spatial compartmentalization of these D1-MSN populations within the NAc. Finally, analysis of published NAc snRNA-seq datasets from non-human primates and humans demonstrated conservation of MSN subtypes across rat and higher order mammals, and further highlighted cell type-specific transcriptional differences across the NAc and broader striatum. These results highlight the utility in using snRNA-seq to characterize both cell type heterogeneity and cell type-specific responses to cocaine and provides a useful resource for cross-species comparisons of NAc cell composition.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103849"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576556","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":"Neuronal endoplasmic reticulum architecture and roles in axonal physiology","authors":"Klaas Yperman ,&nbsp;Marijn Kuijpers","doi":"10.1016/j.mcn.2023.103822","DOIUrl":"10.1016/j.mcn.2023.103822","url":null,"abstract":"<div><p>The endoplasmic reticulum (ER) is the largest membrane compartment within eukaryotic cells and is emerging as a key coordinator of many cellular processes. The ER can modulate local calcium fluxes and communicate with other organelles like the plasma membrane. The importance of ER in neuronal processes such as neurite growth, axon repair and neurotransmission has recently gained much attention. In this review, we highlight the importance of the ER tubular network in axonal homeostasis and discuss how the generation and maintenance of the thin tubular ER network in axons and synapses, requires a cooperative effort of ER-shaping proteins, cytoskeleton and autophagy processes.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103822"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9575318","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":"Chemogenetic inhibition of TrkB signalling reduces phrenic motor neuron survival and size","authors":"Matthew J. Fogarty,&nbsp;Debanjali Dasgupta,&nbsp;Obaid U. Khurram,&nbsp;Gary C. Sieck","doi":"10.1016/j.mcn.2023.103847","DOIUrl":"10.1016/j.mcn.2023.103847","url":null,"abstract":"<div><p><span><span><span>Brain derived neurotrophic factor (BDNF) signalling through its high-affinity </span>tropomyosin receptor kinase B (TrkB) is known to have potent effects on </span>motor neuron<span> survival and morphology during development and in neurodegenerative diseases. Here, we employed a novel 1NMPP1 sensitive </span></span><em>TrkB</em>^{<em>F616</em>} rat model to evaluate the effect of 14 days inhibition of TrkB signalling on phrenic motor neurons (PhMNs). Adult female and male <em>TrkB</em>^{<em>F616</em>}<span> rats were divided into 1NMPP1 or vehicle treated groups. Three days prior to treatment, PhMNs in both groups were initially labeled via intrapleural injection of Alexa-Fluor-647 cholera toxin<span> B (CTB). After 11 days of treatment, retrograde axonal uptake/transport was assessed by secondary labeling of PhMNs by intrapleural injection of Alexa-Fluor-488 CTB. After 14 days of treatment, the spinal cord was excised 100 μm thick spinal sections containing PhMNs were imaged using two-channel confocal microscopy. TrkB inhibition reduced the total number of PhMNs by ∼16 %, reduced the mean PhMN somal surface areas by ∼25 %, impaired CTB uptake 2.5-fold and reduced the estimated PhMN dendritic surface area by ∼38 %. We conclude that inhibition of TrkB signalling alone in adult </span></span><em>TrkB</em>^{<em>F616</em>} rats is sufficient to lead to PhMN loss, morphological degeneration and deficits in retrograde axonal uptake/transport.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103847"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9615947","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":"Cyclosporine A (CsA) prevents synaptic impairment caused by truncated tau by caspase-3","authors":"Carola Tapia-Monsalves ,&nbsp;Margrethe A. Olesen,&nbsp;Francisca Villavicencio-Tejo,&nbsp;Rodrigo A. Quintanilla","doi":"10.1016/j.mcn.2023.103861","DOIUrl":"10.1016/j.mcn.2023.103861","url":null,"abstract":"<div><p><span><span>During Alzheimer's (AD), tau protein suffers from abnormal post-translational modifications, including cleaving by caspase-3. These tau forms affect synaptic plasticity<span> contributing to the cognitive decline observed in the early stages of AD. In addition, caspase-3 cleaved tau (TauC3) impairs </span></span>mitochondrial dynamics<span> and organelles transport, which are both relevant processes for synapse. We recently showed that the absence of tau expression reverts age-associated cognitive and mitochondrial failure by blocking the mitochondrial permeability transition pore<span> (mPTP). mPTP is a mitochondrial complex involved in calcium regulation and apoptosis. Therefore, we studied the effects of TauC3 against the dendritic spine and </span></span></span>synaptic vesicle formation and the possible role of mPTP in these alterations. We used mature hippocampal mice neurons to express a reporter protein (GFP, mCherry), coupled to full-length human tau protein (GFP-T4, mCherry-T4), and coupled to human tau protein cleaved at D421 by caspase-3 (GFP-T4C3, mCherry-T4C3) and synaptic elements were evaluated.</p><p><span><span>Treatment with cyclosporine A (CsA), an </span>immunosuppressive drug with inhibitory activity on mPTP, prevented </span>ROS<span> increase and mitochondrial depolarization induced by TauC3 in hippocampal neurons. These results were corroborated with immortalized cortical neurons in which ROS increase and ATP loss induced by this tau form were prevented by CsA. Interestingly, TauC3 expression significantly reduced dendritic spine density (filopodia type) and synaptic vesicle number in hippocampal neurons. Also, neurons transfected with TauC3 showed a significant accumulation of synaptophysin protein in their soma. More importantly, all these synaptic alterations were prevented by CsA, suggesting an mPTP role in these negative changes derived from TauC3 expression.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103861"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9575406","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}