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Increased vulnerability of dopaminergic neurons in MPTP-lesioned interleukin-6 deficient mice
Laurel M Bolin1, Iwona Strycharska-Orczyk, Richard Murray
1The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, CA 94089, USA. lbolin@parkinsonsinstitute.org
Abstract:
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.
Insights
Interleukin-6 (IL-6) demonstrates neuroprotective effects in the MPTP-lesion mouse model of Parkinson's disease. Its absence exacerbates dopaminergic neuron loss, indicating IL-6 is crucial for protecting these neurons.
Area of Science:
- Neuroscience
- Immunology
- Neuropharmacology
Background:
- Neuroinflammation is implicated in dopaminergic neuron death.
- The role of Interleukin-6 (IL-6) in this process is not fully understood.
Purpose of the Study:
- To investigate the neuroprotective potential of IL-6 in a mouse model of Parkinson's disease.
- To determine if IL-6 influences nigrostriatal degeneration induced by MPTP.
Main Methods:
- Comparison of nigrostriatal degeneration in Interleukin-6 (IL-6) knockout mice (-/-) versus wild-type mice (+/+) after MPTP administration.
- Assessment of striatal dopamine levels and tyrosine hydroxylase-positive (TH+) cell counts in the substantia nigra.
Main Results:
- MPTP induced significantly greater striatal dopamine depletion in IL-6 (-/-) mice compared to IL-6 (+/+) mice.
- A more substantial loss of TH+ cells in the substantia nigra was observed in IL-6 (-/-) mice.
- Astrocytes in the striatum were identified as the source of IL-6 post-MPTP injection.
Conclusions:
- IL-6 exhibits neuroprotective properties within the nigrostriatal system following MPTP-induced injury.
- The absence of IL-6 increases the vulnerability of dopaminergic neurons to neurotoxic insults.