Abstract
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 γ-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 α-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.
| Original language | English |
|---|---|
| Pages (from-to) | 117-135 |
| Number of pages | 19 |
| Journal | Neuroscience |
| Volume | 133 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2005 |
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Keywords
- α-synuclein
- Aggresome
- Golgi apparatus
- Lewy bodies
- Microtubules
- Parkinson's disease
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Rotenone induces aggregation of γ-tubulin protein and subsequent disorganization of the centrosome : Relevance to formation of inclusion bodies and neurodegeneration. / Diaz-Corrales, F. J.; Asanuma, Masato; Miyazaki, Ikuko; Miyoshi, K.; Ogawa, N.
In: Neuroscience, Vol. 133, No. 1, 2005, p. 117-135.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rotenone induces aggregation of γ-tubulin protein and subsequent disorganization of the centrosome
T2 - Relevance to formation of inclusion bodies and neurodegeneration
AU - Diaz-Corrales, F. J.
AU - Asanuma, Masato
AU - Miyazaki, Ikuko
AU - Miyoshi, K.
AU - Ogawa, N.
PY - 2005
Y1 - 2005
N2 - 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 γ-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 α-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.
AB - 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 γ-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 α-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.
KW - α-synuclein
KW - Aggresome
KW - Golgi apparatus
KW - Lewy bodies
KW - Microtubules
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=18844404686&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18844404686&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2005.01.044
DO - 10.1016/j.neuroscience.2005.01.044
M3 - Article
C2 - 15893636
AN - SCOPUS:18844404686
VL - 133
SP - 117
EP - 135
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 1
ER -