Neuroprotective effects of cystamine in aged parkinsonian mice.
Accumulating evidence suggests an important role of oxidation in pathologies such as Parkinson's disease. Here, we investigated the effects of cystamine, which has shown neuroprotection in animal models of Huntington's disease, in a parkinsonian mouse generated by the toxin MPTP. Aged mice (16 months of age) were assigned to either a 10 or 50 mg/kg/day cystamine treatment administered (1) 2 days prior, during and 14 days after MPTP lesioning or (2) beginning on the day of the MPTP lesion and for the subsequent 14 days. Pre-treatment with lower doses of cystamine (10 mg/kg) revealed increased levels of tyrosine hydroxylase (TH) positive striatal fiber (p<0.01), increased density of TH-immunoreactive cells (p<0.01), increased substantia nigra Nurr1 mRNA levels (p<0.001), and increased density of substantia nigra cells expressing the dopamine transporter (p<0.001) as compared to MPTP treated mice. These results provide strong evidence for neuroprotective properties of cystamine in this animal model of Parkinson's disease.
Tremblay
Marie-Eve
ME
Centre de Recherche en Neurosciences, CHUL, RC-9800, 2705 Boulevard Laurier, Sainte-Foy, Quebec, Canada G1V 4G2.
Saint-Pierre
Martine
M
Bourhis
Emmanuelle
E
Lévesque
Daniel
D
Rouillard
Claude
C
Cicchetti
Francesca
F
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D003538:Cystamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007211:Indoles; D020267:MPTP Poisoning / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009930:Organic Chemicals; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D005452:Fluoresceins; D007211:Indoles; D018696:Neuroprotective Agents; D009930:Organic Chemicals; C435731:fluoro jade; C007293:DAPI; D014446:Tyrosine 3-Monooxygenase; D003538:Cystamine