Neurodegenerative disorders are characterized by progressive loss of specific neurons in the central nervous system. Although they have different etiologies and clinical manifestations, most of them share similar histopathologic characteristics such as the presence of inclusion bodies in both neurons and glial cells, which represent intracellular aggregation of misfolded or aberrant
proteins. In
Parkinson's disease, formation of inclusion bodies has been associated with the aggresome-related process and consequently with the centrosome. However, the significance of the centrosome in the neurodegenerative process remains obscure. In the present study, the morphological and functional changes in the centrosome induced by
rotenone, a common
insecticide used to produce
experimental Parkinsonism, were examined both in vitro and in vivo. Aggregation of
gamma-tubulin protein, which is a component of the centrosome matrix and recently identified in Lewy bodies of
Parkinson's disease, was observed in primary cultures of mesencephalic cells treated with
rotenone.
Rotenone-treated neurons and astrocytes showed enlarged and multiple centrosomes. These centrosomes also displayed multiple aggregates of
alpha-synuclein protein. Neurons with disorganized centrosomes exhibited neurite retraction and microtubule destabilization, and astrocytes showed disturbances of mitotic spindles. The Golgi apparatus, which is closely related to the centrosome, was dispersed in both
rotenone-treated neuronal cells and the substantia nigra of
rotenone-treated rats. Our findings suggested that recruitment of abnormal
proteins in the centrosome contributed to the formation of inclusion bodies, and that
rotenone markedly affected the structure and function of the centrosome with consequent induction of cytoskeleton disturbances, disassembly of the Golgi apparatus and collapse of neuronal cells.