Midkine, a new neurotrophic factor, is present in glial cytoplasmic inclusions of multiple system atrophy brains

S. Kato, Takao Shinozawa, Miki Takikawa, Masako Kato, Asao Hirano, Akira Awaya, Eisaku Ohama

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The glial cytoplasmic inclusion (GCI) is a histological hallmark for multiple system atrophy (MSA): these inclusions are found in oligodendrocytes and consist of abnormal granule-coated fibrils of approximately 24- to 40-nm diameter. To clarify the significance of the presence of midkine (MK) in these GCIs, we carried out immunohistochemical, electron and immunoelectron microscopical, and Western blot analyses of MSA brains using a monoclonal antibody against the C-terminal region of human MK. Immunohistochemically, most of the GCIs were intensely stained by the antibody to MK. Electron and immunoelectron microscopy showed that the GCIs were composed of MK-positive granule-coated fibrils that were essential constituents of these inclusions. No significant MK immunoreactivity was observed in oligodendrocytes, astrocytes and neurons of the normal control subjects. The presence of MK in MSA brain but not in normal brain was confirmed by Western blotting. Together with the fact that MK is associated with fetal morphogenesis during the midgestation period, the presence of MK immunoreactivity in oligodendroglial GCIs may suggest the existence of a repair mechanism on the basis of morphogenesis in the degenerated oligodendrocytes themselves as well as the affected neurons and their axons through the oligodendrocyte-axon-neuron relationship.

Original languageEnglish (US)
Pages (from-to)481-489
Number of pages9
JournalActa Neuropathologica
Volume100
Issue number5
DOIs
StatePublished - 2000

Fingerprint

Multiple System Atrophy
Inclusion Bodies
Nerve Growth Factors
Neuroglia
Oligodendroglia
Brain
Morphogenesis
Neurons
Axons
Western Blotting
Immunoelectron Microscopy
midkine
Systems Analysis
Astrocytes
Electron Microscopy
Monoclonal Antibodies
Electrons
Antibodies

Keywords

  • Glial cytoplasmic inclusion
  • Granule-coated fibril
  • Midkine
  • Multiple system atrophy
  • Oligodendrocyte

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Midkine, a new neurotrophic factor, is present in glial cytoplasmic inclusions of multiple system atrophy brains. / Kato, S.; Shinozawa, Takao; Takikawa, Miki; Kato, Masako; Hirano, Asao; Awaya, Akira; Ohama, Eisaku.

In: Acta Neuropathologica, Vol. 100, No. 5, 2000, p. 481-489.

Research output: Contribution to journalArticle

Kato, S, Shinozawa, T, Takikawa, M, Kato, M, Hirano, A, Awaya, A & Ohama, E 2000, 'Midkine, a new neurotrophic factor, is present in glial cytoplasmic inclusions of multiple system atrophy brains', Acta Neuropathologica, vol. 100, no. 5, pp. 481-489. https://doi.org/10.1007/s004010000214
Kato, S. ; Shinozawa, Takao ; Takikawa, Miki ; Kato, Masako ; Hirano, Asao ; Awaya, Akira ; Ohama, Eisaku. / Midkine, a new neurotrophic factor, is present in glial cytoplasmic inclusions of multiple system atrophy brains. In: Acta Neuropathologica. 2000 ; Vol. 100, No. 5. pp. 481-489.
@article{be854c89e7eb4cb99faad50ece4d07e6,
title = "Midkine, a new neurotrophic factor, is present in glial cytoplasmic inclusions of multiple system atrophy brains",
abstract = "The glial cytoplasmic inclusion (GCI) is a histological hallmark for multiple system atrophy (MSA): these inclusions are found in oligodendrocytes and consist of abnormal granule-coated fibrils of approximately 24- to 40-nm diameter. To clarify the significance of the presence of midkine (MK) in these GCIs, we carried out immunohistochemical, electron and immunoelectron microscopical, and Western blot analyses of MSA brains using a monoclonal antibody against the C-terminal region of human MK. Immunohistochemically, most of the GCIs were intensely stained by the antibody to MK. Electron and immunoelectron microscopy showed that the GCIs were composed of MK-positive granule-coated fibrils that were essential constituents of these inclusions. No significant MK immunoreactivity was observed in oligodendrocytes, astrocytes and neurons of the normal control subjects. The presence of MK in MSA brain but not in normal brain was confirmed by Western blotting. Together with the fact that MK is associated with fetal morphogenesis during the midgestation period, the presence of MK immunoreactivity in oligodendroglial GCIs may suggest the existence of a repair mechanism on the basis of morphogenesis in the degenerated oligodendrocytes themselves as well as the affected neurons and their axons through the oligodendrocyte-axon-neuron relationship.",
keywords = "Glial cytoplasmic inclusion, Granule-coated fibril, Midkine, Multiple system atrophy, Oligodendrocyte",
author = "S. Kato and Takao Shinozawa and Miki Takikawa and Masako Kato and Asao Hirano and Akira Awaya and Eisaku Ohama",
year = "2000",
doi = "10.1007/s004010000214",
language = "English (US)",
volume = "100",
pages = "481--489",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - Midkine, a new neurotrophic factor, is present in glial cytoplasmic inclusions of multiple system atrophy brains

AU - Kato, S.

AU - Shinozawa, Takao

AU - Takikawa, Miki

AU - Kato, Masako

AU - Hirano, Asao

AU - Awaya, Akira

AU - Ohama, Eisaku

PY - 2000

Y1 - 2000

N2 - The glial cytoplasmic inclusion (GCI) is a histological hallmark for multiple system atrophy (MSA): these inclusions are found in oligodendrocytes and consist of abnormal granule-coated fibrils of approximately 24- to 40-nm diameter. To clarify the significance of the presence of midkine (MK) in these GCIs, we carried out immunohistochemical, electron and immunoelectron microscopical, and Western blot analyses of MSA brains using a monoclonal antibody against the C-terminal region of human MK. Immunohistochemically, most of the GCIs were intensely stained by the antibody to MK. Electron and immunoelectron microscopy showed that the GCIs were composed of MK-positive granule-coated fibrils that were essential constituents of these inclusions. No significant MK immunoreactivity was observed in oligodendrocytes, astrocytes and neurons of the normal control subjects. The presence of MK in MSA brain but not in normal brain was confirmed by Western blotting. Together with the fact that MK is associated with fetal morphogenesis during the midgestation period, the presence of MK immunoreactivity in oligodendroglial GCIs may suggest the existence of a repair mechanism on the basis of morphogenesis in the degenerated oligodendrocytes themselves as well as the affected neurons and their axons through the oligodendrocyte-axon-neuron relationship.

AB - The glial cytoplasmic inclusion (GCI) is a histological hallmark for multiple system atrophy (MSA): these inclusions are found in oligodendrocytes and consist of abnormal granule-coated fibrils of approximately 24- to 40-nm diameter. To clarify the significance of the presence of midkine (MK) in these GCIs, we carried out immunohistochemical, electron and immunoelectron microscopical, and Western blot analyses of MSA brains using a monoclonal antibody against the C-terminal region of human MK. Immunohistochemically, most of the GCIs were intensely stained by the antibody to MK. Electron and immunoelectron microscopy showed that the GCIs were composed of MK-positive granule-coated fibrils that were essential constituents of these inclusions. No significant MK immunoreactivity was observed in oligodendrocytes, astrocytes and neurons of the normal control subjects. The presence of MK in MSA brain but not in normal brain was confirmed by Western blotting. Together with the fact that MK is associated with fetal morphogenesis during the midgestation period, the presence of MK immunoreactivity in oligodendroglial GCIs may suggest the existence of a repair mechanism on the basis of morphogenesis in the degenerated oligodendrocytes themselves as well as the affected neurons and their axons through the oligodendrocyte-axon-neuron relationship.

KW - Glial cytoplasmic inclusion

KW - Granule-coated fibril

KW - Midkine

KW - Multiple system atrophy

KW - Oligodendrocyte

UR - http://www.scopus.com/inward/record.url?scp=0033822464&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033822464&partnerID=8YFLogxK

U2 - 10.1007/s004010000214

DO - 10.1007/s004010000214

M3 - Article

C2 - 11045670

AN - SCOPUS:0033822464

VL - 100

SP - 481

EP - 489

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 5

ER -