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Series GSE157534 Query DataSets for GSE157534
Status Public on Sep 13, 2021
Title Microglia-specific overexpression of alpha-Synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity [single-cell RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Increasing evidence from recent findings in human samples and animal models support the involvement of inflammation in the development of Parkinson’s disease (PD). Nevertheless, it is currently unknown whether microglia activation could also be a primary event leading to neurodegeneration in PD. We have generated a new mouse model with strictly selective alpha-Synuclein (aSYN) accumulation in microglial cells by inducible gene expression through lentiviral transduction in the nigral tissue. Surprisingly, these mice develop progressive and restricted degeneration of dopaminergic (DA) neurons without any sign of aSYN endogenous aggregation. aSYN accumulating microglial cells exhibit a strong inflammatory status with production of pro-inflammatory cytokines and chemokines. Bulk and scRNA-sequencing of the immune cellular infiltrate identify a complex cellular composition with numerous peripheral populations of the innate and adaptive immune system with specific transcriptional signatures. Molecular profiling and functional assessment reveal that intoxicated microglia develop exhausted phagocytosis and high production of oxidative molecules creating a molecular feed-forward vicious cycle with IFNg secreting immune cells infiltrated in the brain parenchyma. In these animals, pharmacological inhibition of the oxidative and nitrosative molecule production is sufficient to attenuate neurodegeneration. These results suggest that aSYN accumulation in microglia exerts selective DA neuronal degeneration by promoting phagocytic exhaustion, excessive toxic environment and selective recruitment of peripheral immune cells.
 
Overall design 1x CTRL (infected with GFP), 1x SNCA3 (CX3-Cre infected with Synuclein-expressing vector)
 
Contributor(s) Massimino L, Bido S, Broccoli V
Citation(s) 34716339
Submission date Sep 04, 2020
Last update date Dec 02, 2021
Contact name Luca Massimino
E-mail(s) admin@lucamassimino.com
Phone +393389039500
Organization name Ospedale San Raffaele
Department Gastroenterology
Street address Via Olgettina, 58
City Milano
State/province MI
ZIP/Postal code 20100
Country Italy
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM4769518 SNCA
GSM4769519 Control
This SubSeries is part of SuperSeries:
GSE157536 Microglia-specific overexpression of alpha-Synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity
Relations
BioProject PRJNA661582
SRA SRP280165

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Supplementary file Size Download File type/resource
GSE157534_RAW.tar 59.5 Mb (http)(custom) TAR (of CLOUPE)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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