Compromised reactive microgliosis in MPTP-lesioned IL-6 KO mice.

Reactive gliosis, the cellular manifestation of neuroinflammation, is a pathological hallmark of neurodegenerative diseases including Parkinson's disease. The persistent gliosis observed in the Parkinson's disease substantia nigra (SN) and in humans and animals exposed to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) may represent a chronic inflammatory response that contributes to pathology. We have previously shown that in the absence of interleukin-6 (IL-6) dopaminergic neurons are more vulnerable to MPTP.

Alpha-synuclein overexpression protects against paraquat-induced neurodegeneration.

Alpha-synuclein is likely to play a role in neurodegenerative processes, including the degeneration of nigrostriatal dopaminergic neurons that underlies Parkinson's disease. However, the toxicological properties of alpha-synuclein remain relatively unknown. Here, the relationship between alpha-synuclein expression and neuronal injury was studied in mice exposed to the herbicide paraquat.

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.