Molecular and Cellular Neuroscience最新文献

{"title":"Epigenomic profiling of mouse nucleus accumbens at single-cell resolution","authors":"Parth Bhatia ,&nbsp;Lite Yang ,&nbsp;Jay X.J. Luo ,&nbsp;Mengyi Xu ,&nbsp;William Renthal","doi":"10.1016/j.mcn.2023.103857","DOIUrl":"10.1016/j.mcn.2023.103857","url":null,"abstract":"<div><p><span>The nucleus accumbens (NAc) is a key brain region involved in reward processing and is linked to multiple neuropsychiatric conditions such as substance use disorder, depression, and chronic pain. Recent studies have begun to investigate NAc gene expression at a single-cell resolution, however, our understanding of the cellular heterogeneity of the NAc </span>epigenomic<span> landscape remains limited. In this study, we utilize single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) to map cell-type-specific differences in chromatin accessibility in the NAc. Our findings not only reveal the transcription factors and putative gene regulatory elements that may contribute to these cell-type-specific epigenomic differences but also provide a valuable resource for future studies investigating epigenomic changes that occur in neuropsychiatric disorders.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103857"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10162453","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":"Consequences of oxygen deprivation on myelination and sex-dependent alterations","authors":"Rafael Bandeira Fabres ,&nbsp;Débora Sterzeck Cardoso ,&nbsp;Brian Aranibar Aragón ,&nbsp;Bruna Petrucelli Arruda ,&nbsp;Pamela Pinheiro Martins ,&nbsp;Juliane Midori Ikebara ,&nbsp;Alexander Drobyshevsky ,&nbsp;Alexandre Hiroaki Kihara ,&nbsp;Luciano Stürmer de Fraga ,&nbsp;Carlos Alexandre Netto ,&nbsp;Silvia Honda Takada","doi":"10.1016/j.mcn.2023.103864","DOIUrl":"10.1016/j.mcn.2023.103864","url":null,"abstract":"<div><p><span>Oxygen deprivation is one of the main causes of morbidity and mortality in newborns, occurring with a higher prevalence in preterm infants, reaching 20 % to 50 % mortality in newborns in the perinatal period<span>. When they survive, 25 % exhibit neuropsychological pathologies, such as learning difficulties, epilepsy, and cerebral palsy. White matter injury is one of the main features found in oxygen deprivation injury, which can lead to long-term functional impairments, including cognitive delay and motor deficits. The </span></span>myelin<span><span> sheath accounts for much of the white matter in the brain by surrounding axons and enabling the efficient conduction of action potentials. Mature oligodendrocytes<span>, which synthesize and maintain myelination, also comprise a significant proportion of the brain's white matter. In recent years, oligodendrocytes and the myelination process have become potential therapeutic targets to minimize the effects of oxygen deprivation on the </span></span>central nervous system. Moreover, evidence indicate that neuroinflammation and apoptotic pathways activated during oxygen deprivation may be influenced by sexual dimorphism. To summarize the most recent research about the impact of sexual dimorphism on the neuroinflammatory state and white matter injury after oxygen deprivation, this review presents an overview of the oligodendrocyte lineage development and myelination, the impact of oxygen deprivation and neuroinflammation on oligodendrocytes in neurodevelopmental disorders, and recent reports about sexual dimorphism regarding the neuroinflammation and white matter injury after neonatal oxygen deprivation.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103864"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10165257","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":"Sexual dimorphism in the dorsal root ganglia of neonatal mice identified by protein expression profiling with single-cell mass cytometry","authors":"Shayla A. Vradenburgh ,&nbsp;Amy L. Van Deusen ,&nbsp;Allison N. Beachum ,&nbsp;Jacqueline M. Moats ,&nbsp;Ashley K. Hirt ,&nbsp;Christopher D. Deppmann ,&nbsp;Austin B. Keeler ,&nbsp;Eli R. Zunder","doi":"10.1016/j.mcn.2023.103866","DOIUrl":"10.1016/j.mcn.2023.103866","url":null,"abstract":"<div><p><span><span>Development of neuronal and glial populations in the dorsal root ganglia (DRG) is required for detection of touch, body position, temperature, and noxious stimuli. While female-male differences in somatosensory perception have been previously reported, no study has examined global sex differences in the abundance of DRG cell types, and the developmental origin of these differences has not been characterized. To investigate whether sex-specific differences in neuronal and </span>glial cell<span> types arise in the DRG during development, we performed single-cell mass cytometry analysis on sex-separated DRGs from 4 separate litter replicates of postnatal day 0 (P0) C57/BL6 mouse pups. In this analysis, we observed that females had a higher abundance of total neurons (p = 0.0266), as well as an increased abundance of TrkB</span></span>⁺ (p = 0.031) and TrkC⁺<span> (p = 0.04) neurons for mechanoreception and proprioception, while males had a higher abundance of TrkA</span>⁺<span> (p = 0.025) neurons for thermoreception and nociception. Pseudotime comparison of the female and male datasets indicates that male neurons are more mature and differentiated than female neurons at P0. These findings warrant further studies to determine whether these differences are maintained across development, and their impact on somatosensory perception.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103866"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156649","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":"CRMP2 conditional knockout changes axonal function and ultrastructure of axons in mice corpus callosum","authors":"Katarzyna Grycel ,&nbsp;Nick Y. Larsen ,&nbsp;Yinghang Feng ,&nbsp;Klaus Qvortrup ,&nbsp;Poul Henning Jensen ,&nbsp;Mishal Fayyaz ,&nbsp;Malene G. Madsen ,&nbsp;Jens Midtgaard ,&nbsp;Zhiheng Xu ,&nbsp;Stine Hasselholt ,&nbsp;Jens R. Nyengaard","doi":"10.1016/j.mcn.2023.103882","DOIUrl":"10.1016/j.mcn.2023.103882","url":null,"abstract":"<div><p>Collapsin response mediator protein 2 (CRMP2) is a member of a protein family, which is highly involved in neurodevelopment, but most of its members become heavily downregulated in adulthood. CRMP2 is an important factor in neuronal polarization, axonal formation and growth cone collapse. The protein remains expressed in adulthood, but is more region specific. CRMP2 is present in adult corpus callosum (CC) and in plastic areas like prefrontal cortex and hippocampus. CRMP2 has been implicated as one of the risk-genes for Schizophrenia (SZ). Here, a CRMP2 conditional knockout (CRMP2-cKO) mouse was used as a model of SZ to investigate how it could affect the white matter and therefore brain connectivity.</p><p>Multielectrode electrophysiology (MEA) was used to study the function of corpus callosum showing an increase in conduction velocity (CV) measured as Compound Action Potentials (CAPs) in acute brain slices. Light- and electron-microscopy, specifically Serial Block-face Scanning Electron Microscopy (SBF-SEM), methods were used to study the structure of CC in CRMP2-cKO mice. A decrease in CC volume of CRMP2-cKO mice as compared to controls was observed. No differences were found in numbers nor in the size of CC oligodendrocytes (OLs). Similarly, no differences were found in myelin thickness or in node of Ranvier (NR) structure. In contrast, abnormally smaller axons were measured in the CRMP2-cKO mice.</p><p>Using these state-of-the-art methods it was possible to shed light on specific parts of the dysconnectivity aspect of deletion of CRMP2 related to SZ and add details to previous findings helping further understanding the disease. This paper substantiates the white matter changes in the absence of CRMP2 and ties it to the role it plays in this complex disorder.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103882"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169072","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":"Genetics and epigenetics approaches as a path to the future of addiction science","authors":"Anne E. West ,&nbsp;Jeremy J. Day","doi":"10.1016/j.mcn.2023.103898","DOIUrl":"10.1016/j.mcn.2023.103898","url":null,"abstract":"","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"127 ","pages":"Article 103898"},"PeriodicalIF":3.5,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10140767","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":"An in-depth association analysis of genetic variants within nicotine-related loci: Meeting in middle of GWAS and genetic fine-mapping","authors":"Chen Mo ,&nbsp;Zhenyao Ye ,&nbsp;Yezhi Pan ,&nbsp;Yuan Zhang ,&nbsp;Qiong Wu ,&nbsp;Chuan Bi ,&nbsp;Song Liu ,&nbsp;Braxton Mitchell ,&nbsp;Peter Kochunov ,&nbsp;L. Elliot Hong ,&nbsp;Tianzhou Ma ,&nbsp;Shuo Chen","doi":"10.1016/j.mcn.2023.103895","DOIUrl":"10.1016/j.mcn.2023.103895","url":null,"abstract":"<div><p><span><span>In the last two decades of Genome-wide association studies (GWAS), nicotine-dependence-related genetic loci<span> (e.g., nicotinic acetylcholine receptor – nAChR subunit genes) are among the most replicable genetic findings. Although GWAS results have reported tens of thousands of </span></span>SNPs<span> within these loci, further analysis (e.g., fine-mapping) is required to identify the causal variants. However, it is computationally challenging for existing fine-mapping methods to reliably identify causal variants from thousands of candidate SNPs based on the posterior inclusion probability. To address this challenge, we propose a new method to select SNPs by jointly modeling the SNP-wise inference results and the underlying structured network patterns of the linkage disequilibrium (LD) matrix. We use adaptive dense subgraph extraction method to recognize the latent network patterns of the LD matrix and then apply group LASSO to select causal variant candidates. We applied this new method to the UK biobank data to identify the causal variant candidates for nicotine addiction. Eighty-one nicotine addiction-related SNPs (i.e.,-log(p) &gt; 50) of nAChR were selected, which are highly correlated (average </span></span><span><math><msup><mi>r</mi><mn>2</mn></msup><mo>&gt;</mo><mn>0.8</mn></math></span>) although they are physically distant (e.g., &gt;200 kilobase away) and from various genes. These findings revealed that distant SNPs from different genes can show higher LD <span><math><msup><mi>r</mi><mn>2</mn></msup></math></span> than their neighboring SNPs, and jointly contribute to a complex trait like nicotine addiction.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"127 ","pages":"Article 103895"},"PeriodicalIF":3.5,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187141","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":"Experience-dependent Tip60 nucleocytoplasmic transport is regulated by its NLS/NES sequences for neuroplasticity gene control","authors":"Ellen M. Armour,&nbsp;Christina M. Thomas,&nbsp;Gabrielle Greco,&nbsp;Akanksha Bhatnagar,&nbsp;Felice Elefant","doi":"10.1016/j.mcn.2023.103888","DOIUrl":"10.1016/j.mcn.2023.103888","url":null,"abstract":"<div><p><span><span><span>Nucleocytoplasmic transport (NCT) in neurons is critical for enabling proteins to enter the nucleus and regulate plasticity genes in response to environmental cues. Such experience-dependent (ED) neural plasticity is central for establishing memory formation and cognitive function and can influence the severity of neurodegenerative disorders like </span>Alzheimer's disease (AD). ED neural plasticity is driven by </span>histone acetylation<span><span> (HA) mediated epigenetic mechanisms that regulate dynamic activity-dependent </span>gene transcription<span> profiles in response to neuronal stimulation. Yet, how histone acetyltransferases (HATs) respond to extracellular cues in the </span></span></span><em>in vivo</em> brain to drive HA-mediated activity-dependent gene control remains unclear. We previously demonstrated that extracellular stimulation of rat hippocampal neurons <em>in vitro</em><span><span> triggers Tip60 HAT nuclear import with concomitant synaptic gene induction. Here, we focus on investigating Tip60 HAT subcellular localization and NCT specifically in neuronal activity-dependent gene control by using the learning and memory </span>mushroom body (MB) region of the </span><em>Drosophila</em> brain as a powerful <em>in vivo</em><span> cognitive model system. We used immunohistochemistry (IHC) to compare the subcellular localization of Tip60 HAT in the </span><em>Drosophila</em> brain under normal conditions and in response to stimulation of fly brain neurons <em>in vivo</em><span> either by genetically inducing potassium channels activation or by exposure to natural positive ED conditions. Furthermore, we found that both inducible and ED condition-mediated neural induction triggered Tip60 nuclear import with concomitant induction of previously identified Tip60 target genes and that Tip60 levels in both the nucleus and cytoplasm were significantly decreased in our well-characterized </span><em>Drosophila</em><span> AD model. Mutagenesis<span> of a putative nuclear localization signal<span> (NLS) sequence and nuclear export signal (NES) sequence that we identified in the </span></span></span><em>Drosophila</em> Tip60 protein revealed that both are functionally required for appropriate Tip60 subcellular localization. Our results support a model by which neuronal stimulation triggers Tip60 NCT <em>via</em><span> its NLS and NES sequences to promote induction of activity-dependent neuroplasticity gene transcription and that this process may be disrupted in AD.</span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"127 ","pages":"Article 103888"},"PeriodicalIF":3.5,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109343","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":"Special issue: Synaptic logistics — Maintenance of synaptic composition, properties and function","authors":"Noam E. Ziv ,&nbsp;Antoine Triller","doi":"10.1016/j.mcn.2023.103885","DOIUrl":"10.1016/j.mcn.2023.103885","url":null,"abstract":"","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"127 ","pages":"Article 103885"},"PeriodicalIF":3.5,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10481269","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":"Identification of cytoskeletal proteins as binding partners of Bri2 BRICHOS domain","authors":"Makoto Shimozawa ,&nbsp;Helene Tigro ,&nbsp;Henrik Biverstål ,&nbsp;Ganna Shevchenko ,&nbsp;Jonas Bergquist ,&nbsp;Ruin Moaddel ,&nbsp;Jan Johansson ,&nbsp;Per Nilsson","doi":"10.1016/j.mcn.2023.103843","DOIUrl":"10.1016/j.mcn.2023.103843","url":null,"abstract":"<div><p>Proteins must fold into three-dimensional structures to execute their biological functions. Therefore, maintenance of protein homeostasis, proteostasis, including prevention of protein misfolding is essential for cellular activity and health. Molecular chaperones are key actors in proteostasis. BRICHOS domain is an intramolecular chaperone that also interferes with several aggregation-prone proteins including amyloid β (Aβ), involved in Alzheimer's disease (AD). To extend the knowledge about Bri2 BRICHOS interactome we here used recombinant human (rh) Bri2 BRICHOS-mCherry fusion protein to probe for potential binding partners. Firstly, exogenously added Bri2 BRICHOS-mCherry was used to stain brain sections of wildtype and amyloid precursor protein (<em>App</em>) knock-in AD mice exhibiting robust Aβ pathology. Unexpectedly, we found that rh Bri2 BRICHOS-mCherry stained the cytoplasm of neurons which are devoid of Aβ deposits. To identify these intraneuronal proteins that bind to the rh Bri2 BRICHOS domain, we performed co-immunoprecipitation (co-IP) of mouse brain hippocampi homogenates using the Bri2 BRICHOS-mCherry probe and analyzed co-IP proteins by LC-MS/MS. This identified several cytoskeletal proteins including spectrin alpha and beta chain, drebrin, tubulin β3, and β-actin as binding partners. The interactions were confirmed by a second round of pulldown experiments using rh Bri2 BRICHOS linked to magnetic beads. The interaction of rh Bri2 BRICHOS and tubulin β3 was further investigated by staining both mouse brain sections and SH-SY5Y neuroblastoma cells with rh Bri2 BRICHOS-mCherry and tubulin β3 immunostaining, which revealed partial co-localization. These data suggest a possible interplay of extracellular chaperone Bri2 BRICHOS domain in the intracellular space including the cytoskeleton.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103843"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9576543","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":"Bilirubin induces microglial NLRP3 inflammasome activation in vitro and in vivo","authors":"Ilkcan Ercan ,&nbsp;Serap Cilaker Micili ,&nbsp;Sila Soy ,&nbsp;Defne Engur ,&nbsp;Kemal Ugur Tufekci ,&nbsp;Abdullah Kumral ,&nbsp;Sermin Genc","doi":"10.1016/j.mcn.2023.103850","DOIUrl":"10.1016/j.mcn.2023.103850","url":null,"abstract":"<div><p><span><span>Despite current advancements in neonatal care, hyperbilirubinemia resulting in bilirubin-induced neurological dysfunction (BIND) continues to be one of the major reasons of mortality or lifelong disability. Although the exact mechanisms underlying brain injury upon bilirubin exposure remains unelucidated, inflammation is considered to be one of the major contributors to BIND. This study investigates the role of the </span>NLRP3<span> inflammasome in bilirubin-induced injury using </span></span><em>in vitro</em> and <em>in vivo</em> models. We successfully demonstrated that the upregulation of NLRP3 expression is significantly associated with the release of active caspase-1 and IL-1β in N9 microglial cells exposed to bilirubin. Functional <em>in vitro</em><span> experiments with NLRP3 siRNA confirms that bilirubin-induced inflammasome activation and cell death are mediated by the NLRP3 inflammasome. Following injection of bilirubin into the </span><span><em>cisterna magna</em></span><span> of a neonatal mouse, activation of the NLRP3 inflammasome and microglia<span> were determined by double staining with Iba1-NLRP3 and Iba1-Caspase-1. Upon injection of bilirubin into the </span></span><em>cisterna magna</em>, neuronal loss was significantly higher in the wild-type mouse compared to <em>Nlrp3</em>^{<em>−/−</em>} and <em>Caspase-1</em>^{<em>−/−</em>} strains. Collectively, these data indicate that NLRP3 inflammasome has a crucial role in microglial activation and bilirubin-induced neuronal damage.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"125 ","pages":"Article 103850"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9579628","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}