Cortical astroglia transcriptomic dysregulation in the G93A SOD1 ALS mouse model
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ABSTRACT:
PROVIDER: PRJNA435616 | ENA |
REPOSITORIES: ENA
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Project description:Astroglia are the most abundant cell type in the central nervous system. They play essential roles in the homeostasis of the CNS. Astroglia are extremely diverse. In Amyotrophic Lateral Sclerosis (ALS) astroglia in spinal cord undergo dramatic transcriptomic dysregulation. However there is little to no data on the effects that cortical astroglia undergo during ALS pathogenesis. In this study we isolated pure cortical astroglia in end stage ALS mice. We performed microarray analysis and discovered dysregulated pathways and genetic markers. This may serve as a database for scientists to understand the effects that abnormal cortical astroglia have on cortical motor neurons and overall ALS pathology.
2019-04-30 | GSE111031 | GEO
Project description:The role of glia in amyotrophic lateral sclerosis (ALS) is undeniable. Their disease-related activity has been extensively studied in the spinal cord, but only partly in the brain. We present herein a comprehensive study of glia in the motor cortex of SOD1(G93A) mice – a widely used model of ALS. Using single-cell RNA sequencing (scRNA-seq) and immunohistochemistry, we inspected astrocytes, microglia and oligodendrocytes, in four stages of the disease, respecting the factor of sex. We report insignificant motor neuron loss in the cortex, and likewise, minimal changes of glia throughout the disease progression and regardless of sex. Pseudobulk and single-cell analyses revealed subtle disease-related transcriptional alterations at the end-stage in microglia and oligodendrocytes, which were supported by immunohistochemistry. Therefore, our data conclusively prove that the SOD1(G93A) mouse motor cortex does not recapitulate the disease in patients, and we recommend the use of a different model for future studies of the cortical ALS pathology.
2023-04-21 | GSE206330 | GEO
Project description:Expression profiling of spinal cord from SOD1(G93A) mice and age matched controls at ages 28, 42, 56, 70,98,112, and 126 days of age. We used microarrays to determine differential gene expression throughout disease progression in the spinal cord of mutant SOD1(G93A) model of ALS.
2009-10-17 | GSE18597 | GEO
Project description:Extracellular vesicles (EVs) are secreted by myriad cells in culture and also by unicellular organisms, and their identification in mammalian fluids suggests that EV release also occurs at the organism level. However, although it is clearly important to better understand EVs' roles in organismal biology, EVs in solid tissues have received little attention. Here, we modified a protocol for EV isolation from primary neural cell culture to collect EVs from frozen whole murine and human neural tissues by serial centrifugation and purification on a sucrose gradient. Quantitative proteomics comparing brain-derived EVs from nontransgenic (NTg) and a transgenic amyotrophic lateral sclerosis (ALS) mouse model, superoxide dismutase 1 (SOD1) G93A , revealed that these EVs contain canonical exosomal markers and are enriched in synaptic and RNA-binding proteins. The compiled brain EV proteome contained numerous proteins implicated in ALS, and EVs from SOD1 G93A mice were significantly depleted in myelin-oligodendrocyte glycoprotein compared with those from NTg animals. We observed that brain- and spinal cord–derived EVs, from NTg and SOD1 G93A mice, are positive for the astrocyte marker GLAST and the synaptic marker SNAP25, whereas CD11b, a microglial marker, was largely absent. EVs from brains and spinal cords of the SOD1 G93A ALS mouse model, as well as from human SOD1 familial ALS patient spinal cord, contained abundant misfolded and nonnative disulfide-cross-linked aggregated SOD1. Our results indicate that CNS-derived EVs from an ALS animal model contain pathogenic disease-causing proteins and suggest that brain astrocytes and neurons, but not microglia, are the main EV source.
2020-09-11 | PXD021396 | Pride
Project description:Expression profiling of spinal cord from SOD1(G93A) mice and age matched controls at ages 28, 42, 56, 70,98,112, and 126 days of age. We used microarrays to determine differential gene expression throughout disease progression in the spinal cord of mutant SOD1(G93A) model of ALS. Samples were collected from male B6SJL SOD1(G93A) and age matched controls. 3 samples were collected representing each genotype and age group for RNA extraction and hybridization on Affymetrix microarrays.
2009-10-17 | E-GEOD-18597 | biostudies-arrayexpress
Project description:Astroglia are the most abundant glia cell in the central nervous system, playing essential roles in maintaining homeostasis. Key functions of astroglia include, but are not limited to, neurotransmitter recycling, ion buffering, immune modulation, neurotrophin secretion, neuronal synaptogenesis and elimination, and blood-brain barrier maintenance. In neurological diseases, it is well appreciated that astroglia play crucial roles in the disease pathogenesis. In amyotrophic lateral sclerosis (ALS), a motor neuron degenerative disease, astroglia in the spinal cord and cortex downregulate essential transporters, among other proteins, that exacerbate disease progression. Spinal cord astroglia undergo dramatic transcriptome dysregulation. However, in the cortex, it has not been well studied what effects glia, especially astroglia, have on upper motor neurons in the pathology of ALS. To begin to shed light on the involvement and dysregulation that astroglia undergo in ALS, we isolated pure grey-matter cortical astroglia and subjected them to microarray analysis. We uncovered a vast number of genes that show dysregulation at end-stage in the ALS mouse model, G93A SOD1. Many of these genes play essential roles in ion homeostasis and the Wnt-signaling pathway. Several of these dysregulated genes are common in ALS spinal cord astroglia, while many of them are unique. This database serves as an approach for understanding the significance of dysfunctional genes and pathways in cortical astroglia in the context of motor neuron disease, as well as determining regional astroglia heterogeneity, and providing insight into ALS pathogenesis.
| S-EPMC6444185 | biostudies-literature
Project description:Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that progressively debilitates neuronal cells that control voluntary muscle activity. In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1-G93A) skeletal muscle is one of the tissues affected early by mutant SOD1 toxicity. Fast-twitch and slow-twitch muscles are differentially affected in ALS patients and in the SOD1-G93A model, fast-twitch muscles being more vulnerable. We used miRNA microarrays to investigate miRNA alterations in fast-twitch (EDL) and slow-twitch (soleus) skeletal muscles of symptomatic SOD1-G93A animals and their age-matched wild type littermates.
2014-03-04 | GSE55507 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease that progressively debilitates neuronal cells that control voluntary muscle activity. In a mouse model of ALS that expresses mutated human superoxide dismutase 1 (SOD1-G93A) skeletal muscle is one of the tissues affected early by mutant SOD1 toxicity. Fast-twitch and slow-twitch muscles are differentially affected in ALS patients and in the SOD1-G93A model, fast-twitch muscles being more vulnerable. We used miRNA microarrays to investigate miRNA alterations in fast-twitch (EDL) and slow-twitch (soleus) skeletal muscles of symptomatic SOD1-G93A animals and their age-matched wild type littermates. At age of 90 days RNA was extracted from extensor digitorum longus (EDL) and soleus (SOL) muscles of male SOD1-G93A animals and their age-matched wild type male littermates. RNA was hybridized on Affymetrix Multispecies miRNA-2_0 Array.
2014-03-04 | E-GEOD-55507 | biostudies-arrayexpress
Project description:Whole-genome profiling of SH-SY5Y cells was done on neuroblastoma SH-SY5Y stably transfected with cDNAs coding for SOD1WT or the mutant SOD1(G93A) protein.
2010-12-22 | GSE21298 | GEO
Project description:Whole-genome profiling of SH-SY5Y cells was done on neuroblastoma SH-SY5Y stably transfected with cDNAs coding for SOD1WT or the mutant SOD1(G93A) protein. Five wt SOD versus five mutant SOD
2010-12-22 | E-GEOD-21298 | biostudies-arrayexpress