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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
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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.
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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.
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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
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Department |
IMCB
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Lab |
Ernesto Guccione
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Street address |
61 Biopolis Drive
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City |
Singapore |
ZIP/Postal code |
138673 |
Country |
Singapore |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (4)
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Relations |
BioProject |
PRJNA195902 |
SRA |
SRP020468 |