Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopamine neuron loss in the nigrostriatal pathway that shows greater incidence in men than women. The mechanisms underlying this gender bias remain elusive, although one possibility is that androgens may increase dopamine neuronal vulnerability to oxidative stress. Motor impairment can be modeled in rats receiving a unilateral injection of 6-hydroxydopamine (6-OHDA), a neurotoxin producing nigrostriatal degeneration. To investigate the role of androgens in PD, we compared young (2 months) and aged (24 months) male rats receiving gonadectomy (GDX) and their corresponding intact controls. One month after GDX, rats were unilaterally injected with 6-OHDA, and their motor impairment and asymmetry were assessed 2 weeks later using the cylinder test and the amphetamine-induced rotation test. Plasma samples were also collected to assess the concentration of testosterone and advanced oxidation protein products, a product of oxidative stress. GDX decreased lesion-induced asymmetry along with oxidative stress and increased amphetamine-induced rotations. These results show that GDX improves motor behaviors by decreasing motor asymmetry in 6-OHDA-treated rats, an effect that may be ascribed to increased release of striatal dopamine and decreased oxidative stress. Collectively, the data support the hypothesis that androgens may underlie the gender bias observed in PD.
Bibliographical noteFunding Information:
We would like to thank Drs. Yi Wen, Shaohua Yang, Carmen Hinojosa-Laborde, J. Thomas Cunningham, Marilyn Y. McGinnis, and Ms. Wendy Underwood for their excellent technical assistance and advice. This work was supported by the following grants: NIH F32 NS061417 and AHA BGIA4180116 to R.L.C., NIH AG022550 to M.S., and NIH NS050401 to A.G.
- Motor function
- Oxidative stress
- Substantia nigra