title: Riluzole neuroprotection in a Parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation.
abstract: 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.
authors.affiliation: King's College London, Wolfson Centre for Age-Related Diseases, Guy's Campus, London SE1 1UL, UK.
authors.forename: Marica
authors.initials: M
authors.lastname: Carbone
authors.forename: Susan
authors.initials: S
authors.lastname: Duty
authors.forename: Marcus
authors.initials: M
authors.lastname: Rattray
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005911:Gliosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology* / Q000627:therapeutic use; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018696:Neuroprotective Agents; C493395:Slc1a2 protein, rat; D019782:Riluzole; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase