Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA211731 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The loss of Tmem106b results in an age-dependent loss of cerebellar Purkinje cells accompanied with motor function deficits. Tmem106b deficiency also results in lysosomal enlargement in both Purkinje cells and microglia, and increased neuroinflammation including complement system activation. These data suggest that, in addition to myelination, Tmem106b also plays important role in maintaining the health and survival of cerebellar Purkinje cells during aging.
2021-01-20 | GSE165105 | GEO
Project description:Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia and neurodegeneration, often in cerebellar Purkinje neurons. A SCA1 mouse model, Pcp2-ATXN1[30Q]D776, has severe ataxia in absence of progressive Purkinje neuron degeneration and death. Previous RNA-seq analyses identified cerebellar up-regulation of the peptide hormone Cholecystokinin (Cck) in Pcp2-ATXN1[30Q]D776 mice. Importantly, absence of Cck1 receptor (Cck1R) in Pcp2-ATXN1[30Q]D776 mice confers a progressive disease with Purkinje neuron death. A Cck1R agonist, A71623 administered to Pcp2-ATXN1[30Q]D776;Cck-/- and Pcp2-AXTN1[82Q] mice dampened Purkinje neuron pathology and associated deficits in motor performance. In addition, A71623 administration improved motor performance of Pcp2-ATXN2[127Q] SCA2 mice. Moreover, the Cck1R agonist A71623 corrected mTORC1 signaling and improved expression of calbindin in cerebella of AXTN1[82Q] and ATXN2[127Q] mice. These results indicate that manipulation of the Cck-Cck1R pathway is a potential therapeutic target for treatment of diseases involving Purkinje neuron degeneration.
2022-01-11 | GSE180969 | GEO
Project description:Cerebellar circuitry is critical for balance and motor control among a wide array of functions and largely consists of granule and Purkinje neurons. Bergmann glia in the cerebellum form distinct morphological structures that facilitate granule neuron migration during development and that maintain the cerebellar organization and functional integrity. At present, molecular control of the formation and morphogenesis of Bergmann glia remains obscure. In this study, we found that Zeb2 (a.k.a. Sip1 or Zfhx1b), a Mowat-Wilson syndrome-associated transcriptional regulator, is highly restricted to Bergmann glia and is essential for their development and maturation. The mice with Zeb2 ablation in the cerebellar neural progenitor exhibit dysgenesis of cerebellar cortical lamination and locomotion defects. Deletion of Zeb2 markedly reduced Bergmann glial proliferation, differentiation and the establishment of the normal radial scaffold, disrupting migration of granule cell progenitors from external to internal granular layers. Transcriptome profiling indicated that Zeb2 regulates multiple pathways including FGF and Notch signaling as well as axonal guidance cues including Netrin G2 and Gdf10 to control Bergmann glial development. Our data reveal that Zeb2 acts as a transcriptional integrator of diverse signaling pathways to regulate the formation and morphogenesis of Bergmann glia ensuring maintenance of cerebellar integrity, suggesting that Zeb2 dysfunction in Bergmann glia might contribute to motor deficits in Mowat-Wilson syndrome.
2018-06-25 | GSE84098 | GEO
Project description:Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensively transcriptomic landscape of BG. Here, high temporal-resolution investigation of transcriptomes with FACS-sorted BG revealed the dynamic of genes within given functions and pathways enabled BG to assist neural migration and construct neuron-glia network. We found the peak time of GCs migration (P7-10) was strikingly coincided with the downregulation of extracellular matrix (ECM) related genes by prevailing transcriptional repression, and the disrupting of which by Setdb1 ablation at P7-10 in BG led to the significant migration defect of GCs by abnormal ECM expression emphasizing the criticality of Nfix-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo. Thus, BG’s transcriptomic landscapes offer an insight into the mechanism by which BG are in-depth integrated in cerebellar neural network.
2021-04-14 | GSE155872 | GEO
Project description:Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensively transcriptomic landscape of BG. Here, high temporal-resolution investigation of transcriptomes with FACS-sorted BG revealed the dynamic of genes within given functions and pathways enabled BG to assist neural migration and construct neuron-glia network. We found the peak time of GCs migration (P7-10) was strikingly coincided with the downregulation of extracellular matrix (ECM) related genes by prevailing transcriptional repression, and the disrupting of which by Setdb1 ablation at P7-10 in BG led to the significant migration defect of GCs by abnormal ECM expression emphasizing the criticality of Nfix-Setdb1 mediated H3K9me3 repressive complex for the precise regulation of GCs migration in vivo. Thus, BG’s transcriptomic landscapes offer an insight into the mechanism by which BG are in-depth integrated in cerebellar neural network.
2021-04-14 | GSE155871 | GEO
Project description:At present, the underlying neuronal mechanisms leading to an autism spectrum disorder (ASD) diagnosis have not been identified. However, studies from human postmortem ASD brains have consistently revealed disruptions in cerebellar circuitry, specifically with a reduction in Purkinje cell (PC) number and size. Alterations in cerebellar circuitry would have important implications for information processing within the cerebellum and affect a wide range of human motor and non-motor behaviors. Laser capture microdissection was performed to obtain pure PC populations from a cohort of postmortem control and ASD cases and transcriptional profiles were compared.
2022-10-01 | GSE211154 | GEO
Project description:The crosstalk between microglia and neurons has been regarded as a crucial process during development. However, this process is largely unknown in cerebellum. The present study probes into the role of Prrc2a, a posttranscriptional regulator, specifically within cerebellar microglia, utilizing a microglia-specific knockout mouse model. Prrc2a emerged as a crucial regulator of microglial function, influencing transcripts pivotal for brain development. Single-cell RNA sequencing underscored transcriptomic shifts in Prrc2a-deleted microglia, revealing an abnormal immune-activate state. Prrc2a deficiency and alteration of cerebellar microglia are associated with reduced mutual interactions, altered Purkinje cell morphology, reduced molecular layer width, and subsequently alteration in neuronal function, and defects in motor balance and coordination. Collectively, this study provides novel insights into the molecular mechanisms governing microglial-neuronal interactions within the cerebellum.
2025-01-16 | GSE257550 | GEO
Project description:Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset cerebellar ataxia caused by mutations in SACS, which encodes the protein sacsin. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament disorganization, and the progressive death of cerebellar Purkinje neurons. It is unclear how the loss of sacsin function causes these deficits, or why they manifest as cerebellar ataxia. Here, we performed multi-omic profiling in sacsin knockout (KO) cells, and identified alterations in microtubule dynamics, protein trafficking, and mislocalization of synaptic and focal adhesion proteins, including multiple integrins. Focal adhesion structure, signaling, and function were affected in KO cells, which could be rescued by reducing levels of PTEN, an overabundant negative regulator of focal adhesion signaling. Purkinje neurons in ARSACS mice possessed mislocalization of ITGA1, and disorganization of synaptic structures in the deep cerebellar nucleus (DCN). Interactome analysis revealed that sacsin regulates protein-protein interactions between structural and synaptic adhesion proteins. Our findings suggest that disrupted trafficking of synaptic adhesion proteins is a causal molecular deficit underlying ARSACS.
2022-10-25 | PXD036906 | Pride
Project description:Staufen2 (Stau2) is an RNA-binding protein that is involved in dendritic spine morphogenesis and function. Several studies have recently investigated the role of Stau2 in the regulation of its neuronal target mRNAs, with particular focus on the hippocampus. Here, we provide evidence for Stau2 expression and function in cerebellar Purkinje cells. We show that Stau2 downregulation (Stau2GT) lead to an increase of the glutamate receptor ionotropic delta subunit 2 (GluD2) in Purkinje cells when animals performed physical activity by voluntary wheel running. Furthermore, Stau2GT mice showed lower performance in motor coordination assays but enhanced motor learning abilities, concomitantly with an increase in dendritic GluD2 expression. Together, our results suggest a novel role of Stau2 in Purkinje cell synaptogenesis in the mouse cerebellum
2019-04-23 | GSE126996 | GEO
Project description:Gb5 is a divergent, evolutionarily-conserved, member of the heterotrimeric G protein b subunit family that is expressed principally in brain and neuronal tissue. Among Gb isoforms, Gb5 is unique in its ability to heterodimerize with members of the R7 subfamily of the regulator of G protein signaling (RGS) proteins that contain G protein-g like (GGL) domains. Previous studies employing Gb5 knockout mice have shown that Gb5 is an essential stabilizer of GGL domain-containing RGS proteins and regulates the deactivation of retinal phototransduction and the proper functioning of retinal bipolar cells. The purpose of this study is to better understand the functions of Gb5 in the brain outside the visual system by employing molecular biology, immunohistochemistry and confocal imaging technologies. We show here that mice lacking Gb5 have a markedly abnormal neurologic phenotype that includes neurobehavioral developmental delay, wide-based gait, motor learning and coordination deficiencies, and hyperactivity. Using immunohistochemical analysis and a green fluorescent reporter of Purkinje cell maturation we show that the phenotype of Gb5-deficient mice includes, in part, delayed development of the cerebellar cortex, an abnormality that likely contributes to the neurobehavioral phenotype. Multiple neuronally-expressed genes are dysregulated in non-cerebellar portion of Gb5 KO mice. Brain tissues(non-cerebellar portion of brain) from WT and KO with three biological replications of mice were collected, frozen in liquid nitrogen, and stored at -70 °C
2011-09-12 | E-GEOD-29082 | biostudies-arrayexpress