Lipopolysaccharide-Induced Microglia Activation Promotes the Survival of Midbrain Dopaminergic Neurons In Vitro

ORIGINAL ARTICLE
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Abstract

Microglia are the resident immune cells of the central nervous system (CNS) and respond to a variety of endogenous and exogenous stimuli in order to restore cell and tissue homeostasis. Lipopolysaccharide (LPS) is one of these exogenous stimuli, constitutes a major component of the outer membrane of Gram-negative bacteria, and binds to the microglial pattern recognition receptor Toll-like receptor 4 (TLR4). LPS-induced microglia activation is believed to promote neurodegeneration by release of neurotoxic factors such as interleukin-1β, tumor necrosis factor α, or nitric oxide. In the present study, we investigated whether the physical presence of microglia is required to promote neurotoxicity and whether microglia-derived factors are essential. Interestingly, we observed that dopaminergic (mDA) neuron survival was only affected in mixed neuron-glia cultures containing microglia but not in neuron-enriched cultures. Moreover, we clearly demonstrate that microglia-conditioned medium (MCM) after LPS treatment increased mDA neuron survival, process numbers as well as process length. The observed protective effects of MCM was rather caused by microglia-derived factors and only partially dependent on the increase in reactive astrocytes. These results indicate that LPS-induced microglia activation does not necessarily have detrimental effects on mDA neurons and further support the hypothesis that activated microglia support neuron survival by release of neurotrophic and neuroprotective factors.

Keywords

mDA neuron LPS Microglia Astrocytes TGFβ 

Notes

Acknowledgements

The authors would like to thank Susanna Glaser for excellent technical support.

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Authors and Affiliations

  1. 1.Department of NeuroscienceMayo Clinic JacksonvilleJacksonvilleUSA
  2. 2.Institute of AnatomyUniversity of RostockRostockGermany
  3. 3.Institute of Anatomy and Cell Biology, Department of Molecular Embryology, Faculty of MedicineUniversity of FreiburgFreiburgGermany

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