9 research outputs found
Congenital Malformations in Offspring of Diabetic Rats: Experimental Study on the Influence of the Diet Composition and Magnesium Intake
The Inhibition of Embryonic Histone Deacetylases as the Possible Mechanism Accounting for Axial Skeletal Malformations Induced by Sodium Salicylate
Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer epothilone D is neuroprotective
The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl mice. MPTP induced a time-and dose-dependent increase in fibres with altered mitochondria distribution, and early changes in cytoskeletal proteins and MT stability. Indeed, we observed significant increases in neuron-specific beta III tubulin and enrichment of deTyr tubulin in dopaminergic neurons. Finally, we showed that repeated daily administrations of the MT stabilizer Epothilone D rescued MT defects and attenuated nigrostriatal degeneration induced by MPTP. These data suggest that alteration of MTs is an early event specifically associated with dopaminergic neuron degeneration. Pharmacological stabilization of MTs may be a viable strategy for the management of parkinsonism