It has become apparent that astrocytes may be important contributors to inflammatory immune responses within the brain in response to microbial challenges. To date, the mechanisms that underlie activation of this major glial cell type by such challenges have not been investigated. In the present study, we present evidence for members of a recently discovered family of receptors for highly conserved microbial components, the Toll-like receptors (TLRs), in isolated cultures of primary murine astrocytes. We describe the low-level constitutive expression of messenger RNA-encoding TLR2, TLR4, TLR5, and TLR9 in resting cultures of these cells. Importantly, the level of expression of messenger RNA for each of these receptors is markedly elevated following exposure to specific bacteria-derived ligands for these receptors. The functional expression of these receptor proteins is further supported by the ability of known ligands for each TLR to induce both message expression and protein secretion of the proinflammatory cytokine, interleukin-6. In addition, the recent availability of antibodies to TLR2 and TLR4 has enabled us to demonstrate directly the presence of these receptors on astrocytes by Western blot and immunofluorescence analysis, respectively. Furthermore, we have confirmed the sensitivity of such receptor expression to ligand stimulation. The present demonstration of Toll-like microbial pattern-recognition receptors on primary astrocytes provides a mechanistic link between bacterial challenge and inflammatory immune responses that may be an important component of the pathologies of bacterially induced inflammatory CNS disorders.

Objective This study describes associations of ozone and fine particulate matter with Parkinson’s disease observed among farmers in North Carolina and Iowa. Methods We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson’s disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants’ geocoded addresses. Results We observed positive associations of Parkinson’s disease with ozone (OR=1.39; 95% CI: 0.98, 1.98) and fine particulate matter (OR=1.34; 95% CI: 0.93, 1.93) in North Carolina but not in Iowa. Conclusion The plausibility of an effect of ambient concentrations of these pollutants on Parkinson’s disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed.