CHANGES IN PHOSPHORYLATION OF TAU DURING ISCHEMIA AND REPERFUSION IN THE RABBIT SPINAL-CORD

The microtubule-associated protein tau plays an important role in the dynamics of microtubule assembly necessary for axonal growth and neuri te plasticity. Ischemia disrupts the neuronal cytoskeleton both by pro moting proteolysis of its components and by affecting kinase and phosp hatase activities that alter its assembly, In this study the effect of ischemia and reperfusion on the expression and phosphorylation of tau was examined in a reversible model of spinal cord ischemia in rabbits . tau was found to be dephosphorylated in response to ischemia with a time course that closely matched the production of permanent paraplegi a. Dephosphorylation of tau was limited to the caudal lumbar spinal co rd. In a similar manner, Ca2+/calmodulin-dependent kinase II activity was reduced only in the ischemic region, Thus, dephosphorylation of ta u is an early marker of ischemia as is the rapid loss of Ca2+/calmodul in-dependent kinase II activity. tau, however, was rephosphorylated ra pidly during reperfusion at site(s) that cause a reduction in its elec trophoretic mobility regardless of the neurological outcome. Alteratio ns in phosphorylation or degradation of tau may affect microtubule sta bility, possibly contributing to disruption of axonal transport but al so facilitating neurite plasticity in a regenerative response.