Riluzole neuroprotection in a parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation

BMC Neuroscience

Marcus Rattray²  Susan Duty¹  Marica Carbone¹ 

[1] King's College London, Wolfson Centre for Age-Related Diseases, Guy's Campus, London SE1 1UL, UK;Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6UB, UK

关键词: 6-hydroxydopamine;    Glial cell;    GFAP;    Parkinson's Disease;    Neuroprotection;    GLT-1;    EAAT2;   

Others  :  1170753
DOI  :  10.1186/1471-2202-13-38

 received in 2011-12-19, accepted in 2012-04-05,  发布年份 2012

【 摘 要 】

Background

Riluzole is a neuroprotective drug used in the treatment of motor neurone disease. Recent evidence suggests that riluzole can up-regulate the expression and activity of the astrocyte glutamate transporter, GLT-1. Given that regulation of glutamate transport is predicted to be neuroprotective in Parkinson's disease, we tested the effect of riluzole in parkinsonian rats which had received a unilateral 6-hydroxydopamine injection into the median forebrain bundle.

Results

Rats were treated with intraperitoneal riluzole (4 mg/kg or 8 mg/kg), 1 hour before the lesion then once daily for seven days. Riluzole produced a modest but significant attenuation of dopamine neurone degeneration, assessed by suppression of amphetamine-induced rotations, preservation of tyrosine hydroxylase positive neuronal cell bodies in the substantia nigra pars compacta and attenuation of striatal tyrosine hydroxylase protein loss. Seven days after 6-hydroxydopamine lesion, reactive astrocytosis was observed in the striatum, as determined by increases in expression of glial fibrillary acidic protein, however the glutamate transporter, GLT-1, which is also expressed in astrocytes was not regulated by the lesion.

Conclusions

The results confirm that riluzole is a neuroprotective agent in a rodent model of parkinson's disease. Riluzole administration did not regulate GLT-1 levels but significantly reduced GFAP levels, in the lesioned striatum. Riluzole suppression of reactive astrocytosis is an intriguing finding which might contribute to the neuroprotective effects of this drug.

【 授权许可】

   
2012 Carbone et al; licensee BioMed Central Ltd.

【 图 表 】

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