Reduced early hypoxic/ischemic brain damage is associated with increased GLT-1 levels in mice expressing mutant (P301L) human tau.

Liao, Guanghong, Miou Zhou, Simon Cheung, James Galeano, Nam Nguyen, Michel Baudry, and Xiaoning Bi. 2009. “Reduced Early Hypoxic/Ischemic Brain Damage Is Associated With Increased GLT-1 Levels in Mice Expressing Mutant (P301L) Human Tau.”. Brain Research 1247: 159-70.

Abstract

Mutations in tau proteins are associated with a group of neurodegenerative diseases, termed tauopathies. To investigate whether over-expressing human tau with P301L mutation also affects stroke-induced brain damage, we performed hypoxia/ischemia (H/I) in young adult P301L tau transgenic mice. Surprisingly, brain infarct volume was significantly smaller in transgenic mice compared to wild-type mice 24 h after H/I induction. TUNEL staining also revealed less brain apoptosis in transgenic mice following H/I. H/I resulted in a significant increase in tau fragments generated by caspase activation and a marked decrease in tau phosphorylation at residue T231 in cortex of wild-type but not transgenic mice. Activation of calpain and caspase-3 following H/I was also reduced in transgenic compared to wild-type mice, as reflected by lower levels of the specific spectrin breakdown products generated by calpain or caspase-3. Finally, basal levels of the glial glutamate transporter, GLT-1, were higher in brains of transgenic as compared to wild-type mice. These results support the idea that enhanced levels of GLT-1 in transgenic mice are responsible for reducing H/I-induced brain damage by decreasing extracellular glutamate accumulation and subsequent calpain and caspase activation.

Last updated on 04/17/2024
PubMed