Saturday, October 29, 2011
Hall 1-2 (San Jose Convention Center)
Long-term exposure to the pesticide paraquat is an environmental factor that increases the risk of Parkinson’s disease. In this present study, we examined the effects of a single dose of paraquat on microglial activation and differences in cytokine production (proinflammatory or anti-inflammatory) in PACAP knockout mice. Pituitary adenylate cyclase activating polypeptide (PACAP) is known for its neuroprotective effects and specifically has been shown to protect dopaminergic neurons in the substantia nigra of the brain in mice models against neurotoxins like 6-hydroxydopamine. PACAP knockout mice were given a single dose of paraquat and sacrificed a week later. Sections of the substantia nigra from paraformaldehyde perfused brains were stained with an antibody against ionized calcium binding adaptor molecule 1 (IBA-1), a marker of microglia. Microglial activation was quantified by measuring cell body diameter and assessed using a bootstrapping method. Expression of genes resulting from proinflammatory cytokine production was measured by quantitative Real-time RT-PCR. Preliminary results from this lab have shown that there is a loss of tyrosine hydroxylase (TH) in the substantia nigra pars compacta of PACAP knockout mice exposed to paraquat. PACAP knockout and wild-type mice both showed the same level of increased microglial activation after acute paraquat exposure compared to the unexposed wild-type. However, PACAP knockout mice showed an increased level of microglial activation without any paraquat exposure. Therefore this suggests that PACAP knockout mice may be more susceptible to paraquat-inducing TH loss due to the presence of previously activated microglia.