Neuroprotective effects of cystamine in aged parkinsonian mice

• DOI: 10.1016/j.neurobiolaging.2005.04.004
• Publication Date: 2005-05-26T11:20:07Z
• Authors: Marie-Ève Tremblay; Martine Saint-Pierre; Emmanuelle Bourhis; Daniel Lévesque; Claude Rouillard; Francesca Cicchetti
• Keywords: Male; 0301 basic medicine; Aging; Dopamine Plasma Membrane Transport Proteins; Indoles; Dose-Response Relationship, Drug; Cystamine; MPTP Poisoning; Cell Count; Fluoresceins; Immunohistochemistry; Corpus Striatum; Drug Administration Schedule; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Neuroprotective Agents; Gene Expression Regulation; Animals; Organic Chemicals; In Situ Hybridization

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.