Abstract |
The aim of this study was to clarify whether autoimmunity against P/Q-type voltage-gated calcium channels (VGCCs) in the cerebellum was associated with the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome (LEMS). We used human autopsy cerebellar tissues from three PCD-LEMS patients and six other disease patients including one with LEMS as the controls. We compared cerebellar P/Q-type VGCC in these patients and controls for the amount and ratio of autoantibody-channel complex using an 125I-omega-conotoxin MVIIC-binding assay with Scatchard analysis, and their distribution using autoradiography. The quantity of cerebellar P/Q-type VGCC measured by Scatchard analysis were reduced in PCD-LEMS patients (63.0 +/- 7.0 fmol/mg, n = 3), compared with the controls (297.8 +/- 38.9 fmol/mg, n = 6). The ratio of autoantibody-VGCC complexes to total P/Q-type VGCCs measured by immunoprecipitation assay were increased in PCD-LEMS patients. We analysed cerebellar specimens by autoradiography using (125)I-omega-conotoxin MVIIC, which specifically binds to P/Q-type VGCCs. In PCD-LEMS cerebellum, the toxin binding sites of P/Q-type VGCCs were markedly reduced compared with controls, especially in the molecular layer, which is the richest area of P/Q-type VGCCs in the normal cerebellum. This suggests that P/Q-type VGCCs of the cerebellar molecular layer is the immunological target in developing PCD-LEMS.
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Authors | Taku Fukuda, Masakatsu Motomura, Yoko Nakao, Hirokazu Shiraishi, Toshiro Yoshimura, Keisuke Iwanaga, Mitsuhiro Tsujihata, Katsumi Eguchi |
Journal | Annals of neurology
(Ann Neurol)
Vol. 53
Issue 1
Pg. 21-8
(Jan 2003)
ISSN: 0364-5134 [Print] United States |
PMID | 12509844
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Autoantibodies
- Calcium Channels, N-Type
- Elapid Venoms
- Iodine Radioisotopes
- omega-Conotoxins
- voltage-dependent calcium channel (P-Q type)
- dendrotoxin
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Topics |
- Aged
- Autoantibodies
(immunology)
- Autoradiography
- Calcium Channels, N-Type
(immunology, metabolism)
- Cerebellar Ataxia
(immunology, metabolism, pathology)
- Cerebellum
(immunology, metabolism, pathology)
- Elapid Venoms
(metabolism, pharmacology)
- Female
- Humans
- Iodine Radioisotopes
- Lambert-Eaton Myasthenic Syndrome
(immunology, metabolism, pathology)
- Male
- Paraneoplastic Cerebellar Degeneration
(immunology, metabolism, pathology)
- omega-Conotoxins
(metabolism, pharmacology)
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