Dephosphorylation of tau during transient forebrain ischemia in the rat

The effect of transient cerebral ischemia on phosphorylation of the microtu bule-associated protein (MAP) tau was investigated using the rat four-vesse l occlusion model. Phosphorylation of tau is proposed to regulate its bindi ng to microtubules, influencing the dynamics of microtubule assembly necess ary for axonal growth and neurite plasticity. In this study, tau was rapidl y dephosphorylated during ischemia in the hippocampus, neocortex, and stria tum. Dephosphorylation of tau was observed within 5 min of occlusion and in creased after 15 min in all three brain regions, regardless of their relati ve vulnerability to the insult. Thus, dephosphorylation of tau is an early marker of ischemia and precedes the occlusion time required to cause extens ive neuronal cell death in this model. On restoration of blood flow for a l ittle as 15 min, tau was phosphorylated at a site(s) that causes a reductio n 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 trans port, but also allowing neurite remodeling in a regenerative response.