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

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.