Rotenone induces aggregation of γ-tubulin protein and subsequent disorganization of the centrosome: Relevance to formation of inclusion bodies and neurodegeneration

F. J. Diaz-Corrales, Masato Asanuma, Ikuko Miyazaki, K. Miyoshi, N. Ogawa

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 languageEnglish
Pages (from-to)117-135
Number of pages19
JournalNeuroscience
Volume133
Issue number1
DOIs
Publication statusPublished - 2005

Fingerprint

Rotenone
Centrosome
Inclusion Bodies
Tubulin
Proteins
Neurons
Golgi Apparatus
Astrocytes
Parkinson Disease
Synucleins
Spindle Apparatus
Primary Cell Culture
Parkinsonian Disorders
Neurites
Substantia Nigra
Insecticides
Cytoskeleton
Microtubules
Neuroglia
Neurodegenerative Diseases

Keywords

  • α-synuclein
  • Aggresome
  • Golgi apparatus
  • Lewy bodies
  • Microtubules
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{176e45b275294c6c8c8ef2777e6e0aae,
title = "Rotenone induces aggregation of γ-tubulin protein and subsequent disorganization of the centrosome: Relevance to formation of inclusion bodies and neurodegeneration",
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.",
keywords = "α-synuclein, Aggresome, Golgi apparatus, Lewy bodies, Microtubules, Parkinson's disease",
author = "Diaz-Corrales, {F. J.} and Masato Asanuma and Ikuko Miyazaki and K. Miyoshi and N. Ogawa",
year = "2005",
doi = "10.1016/j.neuroscience.2005.01.044",
language = "English",
volume = "133",
pages = "117--135",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "1",

}

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 -