Interleukin-18 null mice show diminished microglial activation and reduced dopaminergic neuron loss following acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment.
Recent reports have revealed an involvement of microglial cells in dopaminergic neurodegeneration. In the present study, we tested the hypothesis that interleukin-18 (IL-18) plays a role in the microglial activation. The present study investigated microglial activation and dopaminergic neurodegeneration in substantia nigra pars compacta (SNpc) following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in wild type (WT) and IL-18 knockout (KO) mice. The number of dopaminergic neuron loss in WT mice was significantly decreased 7 days after MPTP treatment compared with IL-18 KO mice. In WT mice microglial activation occurred in the SN at 1 day after MPTP treatment, progressively increased within the SNpc until 7 days post MPTP, and subsided by 14 days. In contrast, in IL-18 KO mice microglial activation occurred in the SN at 1 day post-MPTP, and decreased by 7 days, earlier than in WT mice. The lesser microglial activation and dopaminergic neurodegeneration in the SNpc following MPTP treatment in WT indicates the possibility that IL-18 may participate in microglial activation and dopaminergic neurodegeneration.
Sugama
S
S
Department of Physiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. sugama@nms.ac.jp
Wirz
S A
SA
Barr
A M
AM
Conti
B
B
Bartfai
T
T
Shibasaki
T
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D020382:Interleukin-18 / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D020382:Interleukin-18; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine