Increased vulnerability of dopaminergic neurons in MPTP‐lesioned interleukin‐6 deficient mice

To test the hypothesis that neuroinflammation contributes to dopaminergic neuron death in the MPTP‐lesioned mouse, we compared nigrostriatal degeneration in interleukin (IL)‐6 (+/+) with IL‐6 (–/–) mice. In the absence of IL‐6, a single injection of MPTP (30 mg/kg) resulted in significantly greater striatal dopamine depletion than that measured in IL‐6 (+/+) mice. The observed dopamine depletion was MPTP dose dependent. This loss of striatal dopamine and a significantly greater loss of TH + cells in the substantia nigra pars compacta in IL‐6 (–/–) mice as compared with control IL‐6 (+/+) mice, suggest that IL‐6 is neuroprotective in the MPTP‐lesioned nigrostriatal system. Co‐localization experiments identified striatal astrocytes as the source of IL‐6 in IL‐6 (+/+) mice at 1 and 7 days postinjection of MPTP. The increased sensitivity of dopaminergic neurons to neurotoxicant in the absence of IL‐6, is compatible with a neuroprotective activity of IL‐6 in the injured nigrostriatal system.