17Beta-estradiol reduces nitrotyrosine immunoreactivity and increases SOD1 and SOD2 immunoreactivity in nigral neurons in male mice following MPTP insult.

Emerging evidence suggests the beneficial effects of estrogen on Parkinson's disease (PD), yet the mechanisms of action implicated remain elusive. While experimental evidence suggests that estrogen possesses potent antioxidative properties, it is still unknown whether the hormone exhibits a neuroprotection in a PD animal model through its antioxidant activities. This study therefore investigated the effects of 17beta-estradiol (E2) on the immunoreactivity of nigral neurons and glia for nitrotyrosine (NT, a stable marker for oxidative stress), Cu/Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. Adult male mice were treated with E2 or vehicle for 11 days during which they were injected with MPTP or saline on the sixth day. The brains were collected on day 11 and quantitative immunohistochemistry was used to assess the number of NT-, SOD1- and SOD2-immunoreactive (IR) cells in the substantia nigra pars compacta (SNpc). In saline-treated group, E2 decreased NT-IR neuronal number and raised SOD1 and SOD2 expression in neurons and glia in the SNpc. MPTP induced a significant increase in the number of NT- and SOD2-IR neurons, but decreased the number of SOD1-IR neurons. MPTP also triggered a significant increase of SOD2- and SOD1-IR glial number. E2 pretreatment in MPTP mice reduced the number of NT-IR neurons, increased the number of SOD1- and SOD2-IR neurons, but did not alter the MPTP effect on glia immunoreactive to either SOD. Stimulation of SOD1 and SOD2 expression in nigral neurons suggests that E2 provides neuroprotection against MPTP-induced oxidative stress, partly through its ability to act as an antioxidant.