Publications

Latest publication 06/30/2012

Overexpression of HGF attenuates the degeneration of Purkinje cells and Bergmann

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder associated with cerebellar neurodegeneration caused by expansion of a CAG...

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    [title] => Overexpression of HGF attenuates the degeneration of Purkinje cells and Bergmann
    [paragraph] => Overexpression of HGF attenuates the degeneration of Purkinje cells and Bergmann glia in a knockin mouse model of spinocerebellar ataxia type 7. 
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Authors
S. Noma, W. Ohya-Shimada, M. Kanai, K. Ueda, T. Nakamura et al.

 Lab
Asahikawa Medical University, Asahikawa, Japan ; Osaka University Graduate School of Medicine, Osaka, Japan.
Journal
Neuroscience Research
Abstract
Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder associated with cerebellar neurodegeneration caused by expansion of a CAG repeat in the ataxin-7 gene. Hepatocyte growth factor (HGF), a pleiotrophic growth factor, displays highly potent neurotrophic activities on cerebellar neurons. A mutant c-met/HGF receptor knockin mouse model has revealed a role for HGF in the postnatal development of the cerebellum. The present study was designed to elucidate the effect of HGF on cerebellar neurodegeneration in a knockin mouse model of SCA7 (SCA7-KI mouse). SCA7-KI mice were crossed with transgenic mice overexpressing HGF (HGF-Tg mice) to produce SCA7-KI/HGF-Tg mice that were used to examine the phenotypic differences following HGF overexpression. The Purkinje cellular degeneration is thought to occur via cell-autonomous and non-cell autonomous mechanisms mediated by a reduction of glutamate transporter levels in Bergmann glia. The Purkinje cellular degeneration and reduced expression of glutamate transporters in the cerebellum of SCA7-KI mice were largely attenuated in the SCA7-KI/HGF-Tg mice. Moreover, phenotypic impairments exhibited by SCA7-KI mice during rotarod tests were alleviated in SCA7-KI/HGF-Tg mice. The bifunctional nature of HGF on both Purkinje cells and Bergmann glia highlight the potential therapeutic utility of this molecule for the treatment of SCA7 and related disorders.
BIOSEB Instruments Used
Aron Test or Four Plates Test (LE830),Rotarod (BX-ROD)

Keywords/Topics
Other pathologies; Miscellaneous
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The Four Plates Test is an exclusivity from BIOSEB!
The Aron test allows a quick characterization of putative anxiolytics compounds in naïve animals. A must for studying anxiety, drug screening and phenotyping.
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