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Histopathologic changes induced by the microtubule‐stabilizing agent Taxol in the rat hippocampus in vivo
Author(s) -
MercadoGómez Octavio,
Ferrera Patricia,
Arias Clorinda
Publication year - 2004
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20264
Subject(s) - microtubule , axoplasmic transport , hippocampus , microbiology and biotechnology , biology , cytoskeleton , in vivo , microtubule associated protein , neurite , tau protein , neuroscience , tubulin , cyclin dependent kinase 5 , programmed cell death , phosphorylation , in vitro , cell , apoptosis , pathology , biochemistry , alzheimer's disease , protein kinase a , medicine , mitogen activated protein kinase kinase , disease
Microtubules and their associated proteins play a prominent role in neuronal morphology, axonal transport, neuronal plasticity, and neuronal degeneration. It has been proposed that microtubule damage is sufficient to induce neuronal death. In this regard, the microtubule‐stabilizing agent Taxol could be a useful tool to reproduce some aspects of neurodegenerative diseases associated with disturbances of the cytoskeleton and alterations in axonal transport. Although differential effects of Taxol on neuronal viability have been found in vitro, Taxol toxicity in the central nervous system remains to be addressed. We studied the effects of Taxol on neuronal morphology and viability as well as changes in microtubule‐associated proteins MAP2 and tau in rat hippocampus. Our results show that Taxol induces dose‐dependent neuronal death accompanied by the loss of MAP2 and the presence of dystrophic neurites. Interestingly paired helical filament (PHF)‐1 immunoreactivity, which is associated with a phosphorylated epitope of tau proteins, was induced in the damaged hippocampus. Our results suggest that microtubule dynamics have a role in maintenance of neuronal morphology and survival in vivo, and that modifications in microtubule dynamics, may alter the content and neuronal distribution of MAP2 and promote alterations in the phosphorylation state of tau. © 2004 Wiley‐Liss, Inc.