Abstract
The effect of transient cerebral ischemia on phosphorylation of the microtubule-associated protein (MAP) τ was investigated using the rat four-vessel occlusion model. Phosphorylation of τ is proposed to regulate its binding to microtubules, influencing the dynamics of microtubule assembly necessary for axonal growth and neurite plasticity. In this study, τ was rapidly dephosphorylated during ischemia in the hippocampus, neocortex, and striatum. Dephosphorylation of τ 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 τ 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, τ was phosphorylated at a site(s) that causes a reduction in its electrophoretic mobility. The dephosphorylation/phosphorylation of τ 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.
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Abbreviations
- MAP:
-
microtubule-associated protein
- AD:
-
Alzheimer disease
- PHF:
-
paired helical filaments
- SDS-PAGE:
-
sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- BSA:
-
bovine serum albumin
- TBS:
-
Tris-buffered saline
- MAb:
-
monoclonal antibody
- RSCIM:
-
rabbit spinal cord ischemia model
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Shackelford, D.A., Yeh, R.Y. Dephosphorylation of tau during transient forebrain ischemia in the rat. Molecular and Chemical Neuropathology 34, 103–120 (1998). https://doi.org/10.1007/BF02815073
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DOI: https://doi.org/10.1007/BF02815073