Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-α, interleukin-1β, and nitric oxide

Lipopolysaccharide Induces Cell Death in Cultured Porcine Myenteric Neurons

“…After six days in culture a dramatic increase in the number of VIP-immunoreactive neurons was observed (Fig 1G and H by the addition of NOS inhibitors thus suggesting that nitric oxide (NO) and/or its metabolites play a critical role (12,15). On the other hand, in dopaminergic neuron cultures NO was found not to mediate the cytotoxic action of LPS; this effect was exerted by the release of inflammatory cytokines such as tumour necrosis factor-α (TNFα) and interleukin-1β (IL-1β) (16,21). Increased concentrations of inflammatory cytokines, eventually causing selective white matter injury, have also been described after intracerebral injection of LPS (22,23).…”

“…The LPS-induced cell loss in central neurons has, by some authors been suggested to be mediated via nitric oxide (13,15) while others claim that it is NO-independent (16).…”

An In Vitro Model of Human Dopaminergic Neurons Derived from Embryonic Stem Cells: MPP+ Toxicity and GDNF Neuroprotection

“…Epidemiological data and twin studies suggest that environmental toxins may be important contributors to PD (Di Monte et al, 2002;Di Monte, 2003;Tanner et al, 1999). The dopaminergic neurons of the brain seem to be especially vulnerable to toxic events, as evidenced by their susceptibility to toxic insults, including rotenone, paraquat, and manganese (Betarbet et al, 2000;Thiruchelvam et al, 2000), lipopolysaccharides (Carvey et al, 2003;Gayle et al, 2002), diesel exhaust particles (Block et al, 2004) and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (Davis et al, 1979;Langston et al, 1983). Therefore, an in vitro system for studies of neurotoxicity and neuroprotection in normal human dopaminergic neurons may be especially valuable.…”

Inflammation in Parkinson’s Disease: Causes and Consequences

“…Studies on rat mesencephalic cultures suggest that DA neurons are twice as sensitive to LPS as non-DA neurons and that the toxicity of LPS occurs via microglial activation (Bronstein et al, 1995;Gayle et al, 2002). Although many in vitro studies have supported an involvement of NO in microglial-mediated DA neuronal death after LPS-treatment (Chao et al, 1992;Gibbons & Dragunow, 2006), others have suggested that NO is not involved (Castano et al, 1998;Gayle et al, 2002). The proinflammatory cytokines IL-1 and TNF- are thought to be involved in LPS-mediated toxicity .…”