2012 Fiscal Year Final Research Report
Connexin astrocytopathy in the pathogenesis of demyelination in concentric sclerosis and multiple sclerosis
| Project/Area Number |
23659459
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
KIRA Jun-ichi 九州大学, 医学研究院, 教授 (40183305)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUSHITA Takuya 九州大学, 医学研究院, 学術研究員 (00533001)
YOSHIMURA Satoshi 九州大学, 医学研究院, 共同研究員 (20596390)
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| Project Period (FY) |
2011 – 2012
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| Keywords | コネキシン / 多発性硬化症 / 視神経脊髄炎 / Balo 病 |
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| Research Abstract |
To investigate the relationship between astrocytopathy and demyelination, we examined the expression of connexins (Cx). We pathologically evaluated the expressions of astrocytic Cx43/Cx30 and oligodendroglial Cx47/Cx32 among autopsied cases with demyelinating disorders. In Balo’ s disease (BD), Cx43, Cx32 and Cx47 were extensively diminished. In the leading edge of Balo’s lesions, Cx43 and AQP4 loss preceded Cx47 loss. Three cases with multiple sclerosis (MS) and six with neuromyelitis optica (NMO) showed preferential Cx43 and AQP4 loss far beyond the demyelinated areas, while vasculocentric deposition of immunoglobulins or complements was observed in four of the six NMO cases. Some NMO cases showed preferential myelin-associated glycoprotein (MAG) loss in AQP4- and Cx43-diminished active lesions. Our findings indicate that disruption of Cx gap junction and preferential MAG loss could occur in MS, BD and NMO, and could be a common denominator. Inhibition of Cx hemichannels is a possible therapeutic target for demyelinating disorders
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[Journal Article] Quantitative assays for anti-aquaporin-4 antibody with subclass analysis in neuromyelitis optica2012
Author(s)
Isobe N, Yonekawa T, Matsushita T, Kawano Y, Masaki K, Yoshimura S, Fichna J, Chen S, Furmaniak J, Smith BR, Kira J
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Journal Title
Mult Scler
Volume: 18
Pages: 1541-1551
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[Journal Article] Extensive loss of connexins in Balo's disease: evidence for an auto- antibody- independent astrocytopathy via impaired astrocyte-oligodendrocyte/myelin interaction2012
Author(s)
Masaki K, Suzuki SO, Matsushita T, Yonekawa T, Matsuoka T, Isobe N, Motomura K, Wu XM, Tabira T, Iwaki T, Kira J
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Journal Title
Acta Neuropathol
Volume: 123
Pages: 887-900
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[Journal Article] Apomorphine treatment for Alzheimer's mice promoting amyloid-ssdegradation2011
Author(s)
Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, Motomura K, Soejima N, Yamasaki R, Hashimoto T, Tabira T, LaFerla FM, Kira J
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Journal Title
Ann Neurol
Volume: 69
Pages: 248-256
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[Journal Article] Interleukin-7 receptor alpha gene polymorphism influences multiple sclerosis risk in Asians2011
Author(s)
Fang L, Isobe N, Yoshimura S, Yonekawa T, Matsushita T, Masaki K, Doi H, Ochi K, Miyamoto K, Kawano Y, Kira J
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Journal Title
Neurology
Volume: 76
Pages: 2125-2127
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