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Tau exacerbates excitotoxic brain damage in an animal model of stroke

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE45703 | GEO | 2017/09/01

SECONDARY ACCESSION(S): PRJNA195902

REPOSITORIES: GEO

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Mus musculus

Project description:Tau exacerbates excitotoxic brain damage in an animal model of stroke

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2011-10-04 | E-GEOD-32529 | biostudies-arrayexpress

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