%0 Journal Article
%T Riluzole neuroprotection in a parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation
%A Marica Carbone
%A Susan Duty
%A Marcus Rattray
%J BMC Neuroscience
%D 2012
%I BioMed Central
%R 10.1186/1471-2202-13-38
%X 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.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.The primary pathological event in Parkinson's disease is degeneration of the nigrostriatal dopamine neurons. In Parkinson's disease, corticostriatal and subthalamonigral glutamate systems are hyperactive, and contribute to symptoms and dopamine neuronal death, through the process of "excitotoxicity" [1-3]. Reducing glutamate transmission through activating type III metabotropic glutamate receptors [2,4], blocking type I metabotropic glutamate receptors [5], or blocking postsynaptic AMPA or NMDA receptors [6,7] have been shown to be neuroprotective and reduce motor symptoms in animal models of Parkinson's disease. In general, therefore, anti-glutamate approaches are attractive and promising therapeutically, although they have not yet led to effective clinical drugs.One potential way of regulating glutamate levels, which has been largely overlooked in Parkinson's disease, is by modulating astrocytes. As
%K EAAT2
%K GLT-1
%K Neuroprotection
%K Parkinson's Disease
%K GFAP
%K Glial cell
%K 6-hydroxydopamine
%U http://www.biomedcentral.com/1471-2202/13/38