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Series GSE242450 Query DataSets for GSE242450
Status Public on May 17, 2024
Title Reactive astrocytes enhance neuronal excitability via IGFBP2: pathological effects of P2Y1 receptor upregulation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Reactive astrocytes play a pivotal role in the pathogenesis of neurological diseases; however, their functional phenotype and the downstream molecules by which they modify disease pathogenesis remain unclear. We genetically increased P2Y1 receptor (P2Y1R) expression, which is upregulated in reactive astrocytes in several neurological diseases, in astrocytes to explore its function and the downstream molecule. This astrocyte-specific P2Y1R overexpression caused neuronal hyperexcitability by increasing both astrocytic and neuronal Ca2+ signals. We identified insulin-like growth factor-binding protein 2 (IGFBP2) as a downstream molecule of P2Y1R in astrocytes; IGFBP2 acts as an excitatory signal to cause neuronal excitation. In neurological disease models of epilepsy and stroke, reactive astrocytes upregulated P2Y1R and increased IGFBP2. The present findings identify a novel mechanism underlying astrocyte-driven neuronal hyperexcitability, which is likely to be shared by several neurological disorders, providing new insights into intervention in diverse neurological disorders.
 
Overall design Hippocampal astrocytes were isolated from astrocyte-specific P2Y1 receptor overexpression mice or their littermate control using MACS with anti-mouse astrocyte cell surface antigen-2 (ACSA2)-coated microbeads for RNA collection. 11-week-old male mice were used. Three mice were used for each sample.
 
Contributor(s) Shigetomi E, Koizumi S
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Submission date Sep 06, 2023
Last update date May 17, 2024
Contact name Eiji Shigetomi
E-mail(s) eshigetomi@yamanashi.ac.jp
Phone +81552739504
Organization name University of Yamanashi
Street address 1110 Shimokato
City Chuo
State/province Yamanashi
ZIP/Postal code 4093898
Country Japan
 
Platforms (1)
GPL28457 DNBSEQ-G400 (Mus musculus)
Samples (6)
GSM7763670 Ctrl_1
GSM7763671 Ctrl_2
GSM7763672 Ctrl_3
Relations
BioProject PRJNA1013495

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Supplementary file Size Download File type/resource
GSE242450_gene_expression_FPKM_and_count.txt.gz 791.3 Kb (ftp)(http) TXT
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