Dephosphorylation of tau during transient forebrain ischemia in the rat.
The effect of transient cerebral ischemia on phosphorylation of the microtubule-associated protein (MAP) tau was investigated using the rat four-vessel occlusion model. Phosphorylation of tau is proposed to regulate its binding to microtubules, influencing the dynamics of microtubule assembly necessary for axonal growth and neurite plasticity. In this study, tau was rapidly dephosphorylated during ischemia in the hippocampus, neocortex, and striatum. Dephosphorylation of tau was observed within 5 min of occlusion and increased after 15 min in all three brain regions, regardless of their relative vulnerability to the insult. Thus, dephosphorylation of tau is an early marker of ischemia and precedes the occlusion time required to cause extensive neuronal cell death in this model. On restoration of blood flow for a little as 15 min, tau was phosphorylated at a site(s) that causes a reduction in its electrophoretic mobility. The dephosphorylation/phosphorylation of tau may alter its distribution between axon and cell body, and affect its susceptibility to proteolysis. These changes would be expected to influence microtubule stability, possibly contributing to disruption of axonal transport, but also allowing neurite remodeling in a regenerative response.
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D019579:Neocortex / Q000378:metabolism; D010766:Phosphorylation; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000302:isolation & purification / Q000378:metabolism*