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Series GSE45703 Query DataSets for GSE45703
Status Public on Sep 01, 2017
Title Tau exacerbates excitotoxic brain damage in an animal model of stroke
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Neuronal excitotoxicity induced by aberrant excitation of glutamatergic receptors contributes to brain damage in stroke. Here, we show that tau-deficient (tau-/-) mice are profoundly protected from excitotoxic brain damage and neurological deficits following experimental stroke, using a middle cerebral artery occlusion (MCAO) with reperfusion model. Mechanistically, we show that this protection is due to site-specific inhibition of glutamate-induced and Ras/ERK-mediated toxicity by accumulation of Ras-inhibiting SynGAP1, which resides in a post-synaptic complex with tau. Accordingly, reducing SynGAP1 levels in tau-/- mice abolished the protection from pharmacologically induced excitotoxicity and MCAO-induced brain damage. Conversely, over-expression of SynGAP1 prevented excitotoxic ERK activation in wild-type neurons. Our findings suggest that tau mediates excitotoxic Ras/ERK signaling by controlling post-synaptic compartmentalization of SynGAP1.
Overall design Total RNA was extracted from control and Tau -/- primary neurons from PTZ treated and untreated C57Bl/6 mice. Mice treated with PTZ were injected intraperitoneally at 6 weeks of age. The final libraries were paired end sequenced on Illumina HiSeq 2000.
Contributor(s) Gladbach A, Eersel JV, Bi M, Müller J, Guccione E, Ke YD, Ittner LM
Citation(s) 28883427
Submission date Apr 02, 2013
Last update date May 15, 2019
Contact name Julius Müller
Organization name A*Star Singapore
Department IMCB
Lab Ernesto Guccione
Street address 61 Biopolis Drive
City Singapore
ZIP/Postal code 138673
Country Singapore
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (4)
GSM1112074 PN_wt_sham
GSM1112075 PN_wt_treat
GSM1112076 PN_ko_sham
BioProject PRJNA195902
SRA SRP020468

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Supplementary file Size Download File type/resource
GSE45703_lack_of_response.txt.gz 8.6 Kb (ftp)(http) TXT
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