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.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease; D015850:Interleukin-6 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D015850:Interleukin-6; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine