Alpha-synuclein and tyrosine hydroxylase expression in acute rotenone toxicity

Chronic low-dose (2-3 mg/kg/day) rotenone infusion produces clinical features and biological markers of Parkinson's disease (PD) in some rats. A significant proportion of rats, however, die of acute rotenone toxicity. Most studies have focused on chronic rotenone-infused rats. It has not been established if the animals that die of acute low-dose rotenone toxicity manifest clinical or pathological evidence of PD. In the present study, six rats that received continuous 3 mg/kg/day subcutaneous rotenone infusion, became moribund and were euthanized after five days were compared with ten vehicle infused animals sacrificed 14, 28 or 56 days after placebo infusion. All rotenone-infused rats had significant motor function decline beginning one day after the infusion and progressive worsening in the physical condition until they became severely akinetic, at which point they were euthanized. In the substantia nigra of rotenone-treated rats, four of six had reduced numbers of tyrosine hydroxylase-positive neurons and all six had increased nigral alpha-synuclein expression. Our observations show that even a short duration of low-dose subcutaneous rotenone infusion can induce clinical and pathological markers of PD in some rats. The pathophysiology of the enhanced susceptibility to PD in some animals remains to be established.