Influence of age and gender on cytokine expression in a murine model of Parkinson's disease.

ABSTRACT

OBJECTIVE: The neuroinflammatory reaction has been linked with Parkinson's disease. One of the hypotheses to explain the significance of age and gender (male predominance) effects on neurodegeneration in Parkinson's disease may result from a link between these risk factors and the inflammatory processes. Here, we investigated the expression of inflammatory mediators in relation to 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP)-induced neurodegenerative processes in nigrostriatal pathway in young and aged male and female mice. METHODS AND RESULTS: We simultaneously assessed striatal tyrosine hydroxylase (TH) protein concentrations (Western blotting) and cytokine (TNFalpha, IFNgamma, IL-1beta, IL-6 and TGFbeta(1)) mRNA levels (RT-PCR) in young and aged (2- and 12-month-old) C57BL/6 male and female mice after 6 h, 1, 3, 7, 14, 21 days after MPTP intoxication. Western blotting analysis showed that at the early time points, males showed a greater reduction in striatal TH versus females. Additionally, in contrast to the aged mice, in young males and females the TH concentration gradually increased between the 7th and the 21st day after intoxication. The increases in TNFalpha, IL-1beta and IFNgamma after intoxication were faster in both young and aged males than females. In males (both ages), we observed an increase in TGFbeta(1) at the early time points. In contrast, in females (both ages) TGFbeta(1) was elevated at later time points. MPTP caused an increase in IL-6 in males and females, but this increase was significantly higher in females. CONCLUSIONS: A gender and age skewing of the cytokine gene expression in the striatum after intoxication may be related to the greater susceptibility in males as well as older animals to the detrimental effects of MPTP.