Viral-toxin interactions and Parkinson's disease: poly I:C priming enhanced the neurodegenerative effects of paraquat.

Background: Parkinson's disease (PD) has been linked with exposure to a variety of environmental and immunological insults (for example, infectious pathogens) in which inflammatory and oxidative processes seem to be involved. In particular, epidemiological studies have found that pesticide exposure and infections may be linked with the incidence of PD. The present study sought to determine whether exposure to a viral mimic prior to exposure to pesticides would exacerbate PD-like pathology.

Interferon-γ plays a role in paraquat-induced neurodegeneration involving oxidative and proinflammatory pathways.

Exposure to environmental contaminants, particularly pesticides, may be an important etiological factor in Parkinson's disease (PD); and evidence suggests a role for microglia-dependent inflammatory and oxidative processes in nigrostriatal pathology induced by such toxins. Yet, the events mediating microglial activation and their effects are not fully known. To this end, we hypothesized that the proinflammatory cytokine, interferon-gamma (IFN-γ), may be a prime factor in the pathogenesis of PD, given its critical role in regulating microglial responses to pathogens.

Behavior and pro-inflammatory cytokine variations among submissive and dominant mice engaged in aggressive encounters: moderation by corticosterone reactivity.

Psychosocial stressors contribute to the pathophysiology of affective disorders and variations of cytokine functioning have been implicated in this process. The present investigation demonstrated, in mice, the impact of stressful aggressive encounters on activity levels, plasma corticosterone and cytokine concentrations, and on cytokine mRNA expression within the prefrontal cortex (PFC) and hippocampus. As glucocorticoids have been tied to cytokine variations, mice were subdivided into low or high corticosterone responders, defined in terms of circulating hormone levels 75 min post-confrontation.

Cyclooxygenase-2 deficiency modifies the neurochemical effects, motor impairment and co-morbid anxiety provoked by paraquat administration in mice.

Parkinson's disease and other motor disorders of midbrain basal ganglia dopaminergic functioning are often characterized by alterations of brainstem and limbic systems with accompanying co-morbid anxiety and depressive symptoms. Accumulating evidence suggests that inflammatory processes may play an important role in such neurodegenerative and psychiatric pathology. In this regard, inhibition of the inflammatory enzyme cyclooxygenase-2 (COX-2) was reported to limit the impact of stressors as well as the neurodegenerative effects of dopaminergic toxins.

Inflammatory priming of the substantia nigra influences the impact of later paraquat exposure: Neuroimmune sensitization of neurodegeneration.

Activation of microglia along with the release of inflammatory cytokines and oxidative factors often accompanies toxin-induced degeneration of substantia nigra pars compacta (SNc) dopamine (DA) neurons. Multiple toxin exposure may synergistically influence microglial-dependent DA neuronal loss and, in fact, pre-treatment with one toxin may sensitize DA neurons to the impact of subsequent insults. Thus, we assessed whether priming SNc neurons with the inflammatory agent, lipopolysaccharide (LPS), influenced the impact of later exposure to the pesticide, paraquat, which has been reported to provoke DA loss.