Related Experiment Videos
Dephosphorylation of tau during transient forebrain ischemia in the rat
1Department of Neurosciences, University of California, San Diego, La Jolla 92093-0624, USA. dshakelford@ucsd.edu
Abstract:
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.
Insights
Transient cerebral ischemia rapidly dephosphorylates microtubule-associated protein tau in rat brains. This early change in tau phosphorylation may impact neuronal function and regeneration following blood flow restoration.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Microtubule-associated protein (MAP) tau regulates microtubule dynamics crucial for neuronal structure and plasticity.
- Tau phosphorylation influences its binding to microtubules, affecting axonal growth and neurite remodeling.
- Transient cerebral ischemia poses a significant threat to neuronal integrity and function.
Purpose of the Study:
- To investigate the effect of transient cerebral ischemia on the phosphorylation state of MAP tau.
- To determine if tau dephosphorylation serves as an early indicator of ischemic events.
- To explore the implications of altered tau phosphorylation on neuronal response and potential regeneration.
Main Methods:
- Utilized the rat four-vessel occlusion model to induce transient cerebral ischemia.
- Analyzed tau phosphorylation levels in hippocampus, neocortex, and striatum at various time points post-occlusion.
- Assessed changes in tau electrophoretic mobility upon restoration of blood flow.
Main Results:
- Rapid dephosphorylation of tau was observed within 5 minutes of ischemic insult in all studied brain regions.
- Tau dephosphorylation intensified after 15 minutes of occlusion, preceding significant neuronal cell death.
- Following 15 minutes of reperfusion, tau phosphorylation increased, altering its electrophoretic mobility.
Conclusions:
- Tau dephosphorylation is an early and sensitive marker of transient cerebral ischemia.
- Dynamic changes in tau phosphorylation during ischemia and reperfusion may modulate microtubule stability.
- These alterations could influence axonal transport disruption and potentially facilitate neurite remodeling and regenerative processes.