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Updated: Aug 22, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Interleukin-18 null mice show diminished microglial activation and reduced dopaminergic neuron loss following acute
1Department of Physiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. sugama@nms.ac.jp
Abstract:
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.
Insights
Interleukin-18 (IL-18) may promote microglial activation and dopaminergic neurodegeneration. Wild-type mice showed less neuron loss and different microglial activation patterns than IL-18 knockout mice after MPTP treatment.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cells are implicated in dopaminergic neurodegeneration.
- The role of interleukin-18 (IL-18) in this process is not fully understood.
Purpose of the Study:
- To investigate the role of IL-18 in microglial activation and dopaminergic neurodegeneration.
- To compare MPTP-induced neurodegeneration in wild-type (WT) and IL-18 knockout (KO) mice.
Main Methods:
- MPTP treatment was administered to WT and IL-18 KO mice.
- Microglial activation and dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) were assessed.
- Changes were evaluated at 1, 7, and 14 days post-treatment.
Main Results:
- WT mice exhibited significantly less dopaminergic neuron loss compared to IL-18 KO mice 7 days after MPTP treatment.
- Microglial activation in WT mice peaked at 7 days and subsided by 14 days post-MPTP.
- In contrast, microglial activation in IL-18 KO mice peaked at 1 day and decreased by 7 days post-MPTP.
Conclusions:
- IL-18 appears to play a role in mediating microglial activation and dopaminergic neurodegeneration.
- Reduced neurodegeneration and altered microglial response in WT mice suggest a protective or modulatory effect of endogenous IL-18.
