Apoptosis-inducing factor in nigral dopamine neurons: Higher levels in primates than in mice.

The nigrostriatal dopaminergic pathway is more susceptible to neurodegeneration in primates than in mice, including the neurotoxic effect of MPTP. Apoptosis-inducing-factor was shown to be involved in the pathogenesis of dopaminergic degeneration. We therefore compared its occurrence in nigral dopamine neurons of mice, monkeys, and humans. Paraffin-embedded brain slices, including the SNpc of C57BL/6J mice, rhesus monkeys, and humans, were immunohistochemically labeled for tyrosine hydroxylase (an enzyme of dopamine synthesis), microtubule-associated protein 2 (a neuronal marker), and apoptosis-inducing factor and examined by confocal laser scan microscopy. The amount of apoptosis-inducing factor in TH-containing SN neurons was 15 times higher in monkeys and 50 times higher in humans than in mice in terms of apoptosis-inducing factor immunoreactive neuronal area excluding the nucleus. The difference of apoptosis-inducing factor levels between primates and mice might contribute to the higher sensitivity of primates to MPTP-induced neurodegeneration of their nigrostriatal dopamine system. © 2016 International Parkinson and Movement Disorder Society.