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IL6 protects MN9D cells and midbrain dopaminergic neurons from MPP+-induced neurodegeneration
Björn Spittau1, Xiaolai Zhou, Ming Ming
1Department of Molecular Embryology, Institute for Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Albertstrasse 17, 79104, Freiburg, Germany. bjoern.spittau@anat.uni-freiburg.de
Abstract:
The degeneration of midbrain dopaminergic (mDA) neurons is the hallmark of Parkinson's disease (PD), and several in vivo and in vitro models have been established to resemble the processes occurring during disease progression. One of the most commonly used disease models for PD is the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively kills mDA neurons when applied systemically. In vivo, MPTP intoxication is accompanied by a strong microglia response which is characterised by the release of inflammatory molecules such as tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL6) that are believed to further drive inflammation-mediated degeneration of mDA neurons. Here, we addressed the question whether primary ventral mDA neurons and MN9D cells release cytokines in vitro and how these cytokine profiles change after treatment with MPP(+). Our results demonstrate that both culture models show different cytokine profiles under control conditions indicating that comparisons between both models should be made very carefully. Moreover, MN9D cells released high levels of IL6 and IP10/CXCL10, both of which were down regulated after treatment with MPP(+). MN9D-derived IL6 seems to be important for MN9D survival since neutralisation of endogenous IL6 resulted in degeneration of MN9D cells. Moreover, recombinant IL6 was able to rescue MN9D cells and primary mDA neuron cultures from MPP(+)-induced neurotoxicity, underlining the neuroprotective properties of IL6.
Insights
Parkinson's disease models show that interleukin-6 (IL6) protects midbrain dopaminergic neurons from MPP+-induced toxicity. Neutralizing IL6 caused cell degeneration, highlighting its neuroprotective role in Parkinson's disease research.
Area of Science:
- Neuroscience
- Cell Biology
- Neuroinflammation
Background:
- Parkinson's disease (PD) is characterized by the degeneration of midbrain dopaminergic (mDA) neurons.
- The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model is widely used to study PD, involving mDA neuron loss and inflammatory responses.
- MPTP-induced neurotoxicity involves microglia activation and the release of inflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL6).
Purpose of the Study:
- To investigate cytokine release profiles of primary ventral mDA neurons and MN9D cells in vitro.
- To determine how these cytokine profiles change following MPP+ (the toxic metabolite of MPTP) treatment.
- To elucidate the role of IL6 in MPP+-induced neurotoxicity and neuronal survival.
Main Methods:
- Primary ventral mDA neurons and MN9D cells were cultured in vitro.
- Cells were treated with MPP+ to mimic PD-related neurotoxicity.
- Cytokine release was analyzed, and the effects of IL6 neutralization and recombinant IL6 administration were assessed.
Main Results:
- Primary mDA neurons and MN9D cells exhibited distinct cytokine profiles under basal conditions.
- MPP+ treatment altered cytokine release in MN9D cells, downregulating IL6 and IP10/CXCL10.
- MN9D cell survival was dependent on endogenous IL6, and recombinant IL6 demonstrated neuroprotective effects against MPP+-induced toxicity in both cell types.
Conclusions:
- Distinct cytokine profiles exist between primary mDA neurons and MN9D cells, necessitating careful comparison.
- Interleukin-6 plays a crucial neuroprotective role against MPP+-induced neurotoxicity in both primary mDA neurons and MN9D cells.
- IL6's protective function suggests its therapeutic potential in Parkinson's disease.
