Premium
Increased vulnerability of dopaminergic neurons in MPTP‐lesioned interleukin‐6 deficient mice
Author(s) -
Bolin Laurel M.,
StrycharskaOrczyk Iwona,
Murray Richard,
Langston J. William,
Di Monte Donato
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01131.x
Subject(s) - mptp , substantia nigra , pars compacta , dopaminergic , dopamine , neuroprotection , medicine , nigrostriatal pathway , endocrinology , neuroscience , neuroinflammation , chemistry , biology , inflammation
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.