Molecular and Cellular Neuroscience最新文献

{"title":"Effect of germ-free status on transcriptional profiles in the nucleus accumbens and transcriptomic response to chronic morphine","authors":"Jonathon P. Sens ,&nbsp;Rebecca S. Hofford ,&nbsp;Drew D. Kiraly","doi":"10.1016/j.mcn.2023.103874","DOIUrl":"10.1016/j.mcn.2023.103874","url":null,"abstract":"<div><p><span><span><span>Opioid use disorder is a public health crisis that causes tremendous suffering for patients as well as substantial social and economic costs for society. There are currently available treatments for patients with opioid use disorder, but they remain intolerable or ineffective for many. Thus the need to develop new avenues for therapeutics development in this space is great. Substantial work in models of substance use disorders, including opioid use disorder, demonstrates that prolonged exposure to drugs of abuse leads to marked transcriptional and epigenetic dysregulation in limbic substructures. It is widely believed that these changes in gene regulation in response to drugs are a key driving factor in the perpetuation of drug taking and seeking </span>behaviors. Thus, development of interventions that could shape transcriptional regulation in response to drugs of abuse would be of high value. Over the past decade there has been a surge in research demonstrating that the resident bacteria of the </span>gastrointestinal tract<span>, collectively the gut microbiome, can have tremendous influence on neurobiological and behavioral plasticity. Previous work from our group and others has demonstrated that alterations in the gut microbiome can alter behavioral responses to opioids in multiple paradigms. Additionally, we have previously reported that depletion of the gut microbiome with antibiotics markedly shifts the </span></span>transcriptome<span> of the nucleus accumbens<span> following prolonged morphine exposure. In this manuscript we present a comprehensive analysis of the effects of the gut microbiome on transcriptional regulation of the nucleus accumbens following morphine by utilizing germ-free, antibiotic treated, and control mice. This allows for detailed understanding of the role of the microbiome in regulating baseline transcriptomic control, as well as response to morphine. We find that germ-free status leads to a marked gene dysregulation in a manner distinct to adult mice treated with antibiotics, and that altered gene pathways are highly related to cellular metabolic processes. These data provide additional insight into the role of the gut microbiome in modulating brain function and lay a foundation for further study in this area.</span></span></p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103874"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166564","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":"Profiling transcriptomic responses of human stem cell-derived medium spiny neuron-like cells to exogenous phasic and tonic neurotransmitters","authors":"Ryan W Tam PhD,&nbsp;Albert J. Keung","doi":"10.1016/j.mcn.2023.103876","DOIUrl":"10.1016/j.mcn.2023.103876","url":null,"abstract":"<div><p><span><span><span>Transcriptomic<span> responses to neurotransmitters contribute to the complex processes driving memory and addiction. Advances in both measurement methods and experimental models continue to improve our understanding of this regulatory layer. Here we focus on the experimental potential of stem cell derived neurons, currently the only ethical model that can be used in reductionist and experimentally perturbable studies of human cells. Prior work has focused on generating distinct cell types from human stem cells, and has also shown their utility in modeling development and cellular phenotypes related to </span></span>neurodegeneration<span>. Here we seek an understanding of how stem cell derived neural cultures respond to perturbations experienced during development and disease progression. This work profiles transcriptomic responses of human medium spiny neuron-like cells with three specific goals. We first characterize transcriptomic responses to dopamine and dopamine receptor agonists and antagonists presented in dosing patterns mimicking acute, chronic, and withdrawal regimens. We also assess transcriptomic responses to low and persistent tonic levels of dopamine, </span></span>acetylcholine, and </span>glutamate to better mimic the in vivo environment. Finally, we identify similar and distinct responses between hMSN-like cells derived from H9 and H1 stem cell lines, providing some context for the extent of variability these types of systems will likely pose for experimentalists. The results here suggest future optimizations of human stem cell derived neurons to increase their in vivo relevance and the biological insights that can be garnered from these models.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103876"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10157127","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":"Recovery of motor function is associated with rescue of glutamate biomarkers in the striatum and motor cortex following treatment with Mucuna pruriens in a murine model of Parkinsons disease","authors":"Tanya Denne ,&nbsp;Lila C. Winfrey ,&nbsp;Cindy Moore ,&nbsp;Chase Whitner ,&nbsp;Theresa D'Silva ,&nbsp;Amala Soumyanath ,&nbsp;Lynne Shinto ,&nbsp;Amie Hiller ,&nbsp;Charles K. Meshul","doi":"10.1016/j.mcn.2023.103883","DOIUrl":"10.1016/j.mcn.2023.103883","url":null,"abstract":"<div><p><span>There is growing interest in the use of natural products for the treatment of Parkinson's disease (PD). </span><span><em>Mucuna</em><em> pruriens</em></span><span> has been used in the treatment of humans with PD. The goal of this study was to determine if daily oral treatment with an extract of </span><em>Mucuna pruriens</em><span><span><span>, starting after the MPTP-induced loss of nigrostriatal dopamine in male mice, would result in recovery/restoration of motor function, tyrosine hydroxylase<span> (TH) protein expression in the </span></span>nigrostriatal pathway, or </span>glutamate<span><span> biomarkers in both the striatum and motor cortex. Following </span>MPTP administration, resulting in an 80 % loss of striatal TH, treatment with </span></span><em>Mucuna pruriens</em><span> failed to rescue either striatal TH or the dopamine transporter<span> back to the control levels, but there was restoration of gait/motor function. There was an MPTP-induced loss of TH-labeled neurons in the substantia nigra pars compacta<span> and in the number of striatal dendritic spines, both of which failed to be recovered following treatment with </span></span></span><em>Mucuna pruriens</em>. This <em>Mucuna pruriens</em><span>-induced locomotor recovery following MPTP was associated with restoration of two striatal glutamate transporter proteins<span><span>, GLAST (EAAT1) and EAAC1 (EAAT3), and the </span>vesicular glutamate transporter 2 (Vglut2) within the motor cortex. Post-MPTP treatment with </span></span><em>Mucuna pruriens</em>, results in locomotor improvement that is associated with recovery of striatal and motor cortex glutamate transporters but is independent of nigrostriatal TH restoration.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103883"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166333","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":"Satellite glial cell-secreted exosomes after in-vitro oxaliplatin treatment presents a pro-nociceptive effect for dorsal root ganglion neurons and induce mechanical hypersensitivity in naïve mice","authors":"Liping Zhao ,&nbsp;Shijiang Liu ,&nbsp;Xiaobao Zhang ,&nbsp;Juan Yang ,&nbsp;Mao Mao ,&nbsp;Susu Zhang ,&nbsp;Shiqin Xu ,&nbsp;Shanwu Feng ,&nbsp;Xian Wang","doi":"10.1016/j.mcn.2023.103881","DOIUrl":"10.1016/j.mcn.2023.103881","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;&lt;span&gt;&lt;span&gt;The pathophysiological mechanism underlying chemotherapy-induced neuropathic pain (CINP) remains unclear. Sensory neuronal hypersensitivity in the &lt;/span&gt;dorsal root ganglion&lt;span&gt; (DRG) is essential for the onset and maintenance of chronic pain. Satellite glial cells (SGCs) in the DRG potentially affect the function of &lt;/span&gt;&lt;/span&gt;sensory neurons&lt;span&gt;, possibly by mediating extracellular or paracrine signaling. Exosomes play an essential role in cell-cell communication. However, the role of SGC-secreted exosomes in glia-neuron communication and CINP remains unclear.&lt;/span&gt;&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;&lt;span&gt;&lt;span&gt;&lt;span&gt;SGCs and sensory neurons were cultured from the DRG of mice. The SGCs were treated with 4 μM oxaliplatin for 24 h. Glial fibrillary &lt;/span&gt;acid protein&lt;span&gt;&lt;span&gt; (GFAP) and connexin-43 (Cx-43) expressions in the SGCs were examined with immunocytochemistry (ICC). Enzyme-linked immunosorbent assay (ELISA) detected &lt;/span&gt;cytokine release in the SGCs after oxaliplatin treatment. Subsequently, SGC-secreted exosomes were collected using &lt;/span&gt;&lt;/span&gt;ultracentrifugation&lt;span&gt; and identified by nanoparticle tracking analysis, transmission electron microscopy&lt;span&gt;&lt;span&gt;&lt;span&gt;, and western blotting. Subsequently, DRG neurons were incubated with SGC-secreted exosomes for 24 h. The percentage of &lt;/span&gt;reactive oxygen species (ROS)-positive neurons was detected using flow cytometry, and acid-sensing ion channel 3 (ASIC3) and &lt;/span&gt;transient receptor potential vanilloid 1 (TRPV1) expression were examined by western blotting. SGC-secreted exosomes were intrathecally injected into naïve mice. The mechanical withdrawal threshold was assessed 24, 48, and 72 h following the injection. TRPV1 expression in the DRG was examined 72 h after &lt;/span&gt;&lt;/span&gt;&lt;/span&gt;intrathecal&lt;span&gt;&lt;span&gt; injection. Furthermore, differentially expressed (DE) miRNAs within the SGC-secreted exosomes were detected using &lt;/span&gt;RNA sequencing&lt;span&gt; and bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses were performed to predict the function of the target genes of DE miRNAs. Finally, the DE miRNAs with pain regulation potential were identified in silico.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;&lt;span&gt;&lt;span&gt;After in-vitro oxaliplatin treatment, ICC showed an increase in the immunoreactivity of GFAP and Cx-43 in the SGCs. ELISA results suggested an increased release of tumor necrosis factor-α and &lt;/span&gt;interleukin (IL)-1β, but a decreased release of IL-10. Oxaliplatin treatment increased the secretion of exosomes in the SGCs from 4.34 to 5.99 × 10&lt;/span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;span&gt; (particles/ml). The exosome-specific markers CD9&lt;span&gt;&lt;span&gt; and TSG101&lt;span&gt;&lt;span&gt; were positive, whereas calnexin was negative for the obtained exosomes. Additionally, the SGC-secreted exosomes were endocytosed by DRG neurons after co-incubation. Moreover, after incubati","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103881"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10167107","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":"The Npc2Gt(LST105)BygNya mouse signifies pathological changes comparable to human Niemann-Pick type C2 disease","authors":"Charlotte Laurfelt Munch Rasmussen ,&nbsp;Louiza Bohn Thomsen ,&nbsp;Christian Würtz Heegaard ,&nbsp;Torben Moos ,&nbsp;Annette Burkhart","doi":"10.1016/j.mcn.2023.103880","DOIUrl":"https://doi.org/10.1016/j.mcn.2023.103880","url":null,"abstract":"<div><h3>Introduction</h3><p><span>Niemann-Pick type C2 disease (NP-C2) is a fatal neurovisceral disorder caused by defects in the lysosomal cholesterol transporter protein NPC2. Consequently, cholesterol and other lipids accumulate within the </span>lysosomes, causing a heterogeneous spectrum of clinical manifestations. Murine models are essential for increasing the understanding of the complex pathology of NP-C2. This study, therefore, aims to describe the neurovisceral pathology in the NPC2-deficient mouse model to evaluate its correlation to human NP-C2.</p></div><div><h3>Methods</h3><p><em>Npc2</em>−/− mice holding the LST105 mutation were used in the present study (<em>Npc2</em>^{<em>Gt(LST105)BygNya</em>}). Body and organ weight and histopathological evaluations were carried out in six and 12-week-old <em>Npc2</em><span><span>−/− mice, with a special emphasis on neuropathology. The Purkinje cell<span> (PC) marker calbindin, the astrocytic marker </span></span>GFAP<span><span>, and the microglia<span> marker IBA1 were included to assess PC degeneration and neuroinflammation, respectively. In addition, the pathology of the liver, lungs, and spleen was assessed using </span></span>hematoxylin<span><span> and eosin </span>staining.</span></span></span></p></div><div><h3>Results</h3><p>Six weeks old pre-symptomatic <em>Npc2</em><span>−/− mice showed splenomegaly and obvious neuropathological changes, especially in the cerebellum, where initial PC loss and neuroinflammation were evident. The </span><em>Npc2</em>−/− mice developed neurological symptoms at eight weeks of age, severely progressing until the end-stage of the disease at 12 weeks. At the end-stage of the disease, <em>Npc2</em><span>−/− mice were characterized by growth retardation, tremor, cerebellar ataxia, splenomegaly, foam cell accumulation in the lungs, liver, and spleen, brain atrophy, pronounced PC degeneration, and severe neuroinflammation.</span></p></div><div><h3>Conclusion</h3><p>The <em>Npc2</em>^{<em>Gt(LST105)BygNya</em>} mouse model resembles the pathology seen in NP-C2 patients and denotes a valuable model for increasing the understanding of the complex disease manifestation and is relevant for testing the efficacies of new treatment strategies.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103880"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49858578","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":"The molecular neural mechanism underlying the acceleration of brain aging due to Dcf1 deficiency","authors":"Haicong Zhou ,&nbsp;Jiao Wang ,&nbsp;Tieqiao Wen","doi":"10.1016/j.mcn.2023.103884","DOIUrl":"10.1016/j.mcn.2023.103884","url":null,"abstract":"<div><p><span>Owing to the continuous increase in human life expectancy, the management of aging-related diseases has become an urgent issue. The brain dominates the central nervous system<span>; therefore, brain aging is a key area of aging-related research. We previously uncovered that dendritic cell factor 1 (</span></span><em>Dcf1</em><span>) maintains the stemness of neural stem cells and its expression in </span><em>Drosophila</em> can prolong lifespan, suggesting an association between <em>Dcf1</em><span> and aging; however, the specific underlying neural mechanism remains unclear. In the present study, we show for the first time that hippocampal neurogenesis is decreased in aged </span><em>Dcf1</em>^−/− mice, which leads to a decrease in the number of brain neurons and an increased number of senescent cells. Moreover, astrocytes proliferate abnormally and express elevated mRNA levels of aging-related factors, in addition to displaying increased activation of Akt and Foxo3a. Finally, behavioral tests confirm that aged <em>Dcf1</em>^−/− mice exhibit a significant decline in cognitive abilities related to learning and memory. In conclusion, we reveal a novel mechanism underlying brain aging triggered by <em>Dcf1</em> deficiency at the molecular, cellular, tissue, and behavioral levels, providing a new perspective for the exploration of brain aging.</p></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"126 ","pages":"Article 103884"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166324","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":"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}