Parkinson's disease is a neurodegenerative disorder with uncertain aetiology and ill-defined pathophysiology. Activated microglial cells in the substantia nigra (SN) are found in all animal models of Parkinson's disease and patients with the illness. Microglia may, however, have detrimental and protective functions in this disease. In this study, we tested the hypothesis that a sub-toxic dose of an inflammogen (lipopolysaccharide) can shift microglia to a pro-inflammatory state and exacerbate disease progression in an animal model of Parkinson's disease. Central lipopolysaccharide injection in a degenerating SN exacerbated neurodegeneration, accelerated and increased motor signs and shifted microglial activation towards a pro-inflammatory phenotype with increased interleukin-1β (IL-1β) secretion. Glucocorticoid treatment and specific IL-1 inhibition reversed these effects. Importantly, chronic systemic expression of IL-1 also exacerbated neurodegeneration and microglial activation in the SN. In vitro, IL-1 directly exacerbated 6-OHDA-triggered dopaminergic toxicity. In vivo, we found that nitric oxide was a downstream molecule of IL-1 action and partially responsible for the exacerbation of neurodegeneration observed. Thus, IL-1 exerts its exacerbating effect on degenerating dopaminergic neurons by direct and indirect mechanisms. This work demonstrates an unequivocal association between IL-1 overproduction and increased disease progression, pointing to inflammation as a risk factor for Parkinson's disease and suggesting that inflammation should be efficiently handled in patients to slow disease progression.

Road accidents are a major cause of death, and sleep deprivation affects driving skills. We conducted a cross-sectional study to evaluate sleep habits and accident risk in long-haul truck drivers in Buenos Aires, Argentina. Questionnaires regarding sleep habits, snoring, and daytime sleepiness were administered, and a limited physical examination was performed. We obtained 738 complete answers (response rate 85%). Mean sleep hours during working days was 3.76 (SD 2.40). Mean driving hours was 15.9 (SD 5.60) per day. Frequent sleepiness while driving was reported by 43.7% of responders. Sleepiness while driving was associated with Epworth Sleepiness Scale values >10 (odds ratio 1.85, 95% confidence interval = 1.20-2.85). Snoring was reportea by 71% of drivers and was frequent in 43.8%. Snoring more than 3 times a week (odds ratio 1.73, 95% confidence interval = 1.23-2.44), sleepiness while driving (OR 1.92, 95% confidence interval = 1.08-1.96), and Epworth Sleepiness Scale score > 10 (odds ratio 2.53, 95% confidence interval = 1.61-3.97) were independently associated with reporting of accidents or near accidents. Sleep deprivation and long driving shifts were prevalent in our study. Accident risk was associated with frequent snoring, daytime sleepiness, and reporting of sleepiness at the wheel. This study highlights the need of improving working conditions in this highly exposed population.

Stressful stimuli during pregnancy induce complex effects that influence the development of offspring. These effects can be prevented by environmental manipulations during the early postnatal period. Repeated restraint during the last week of pregnancy was used as a model of prenatal stress, and adoption at birth was used to change the postnatal environment. No differences were found in various physical landmarks, except for testis descent, for which all prenatally stressed pups showed a 1-day delay in comparison with control rats, regardless of the postnatal adoption procedure. Levels of dopamine (DA) D(2) and glutamate (Glu) N-methyl-D-aspartate (NMDA) receptors were differentially regulated in different forebrain regions of cross-fostered adult offspring. Increased concentrations of cortical D(2) receptors detected in stressed pups, raised by a gestationally stressed biological mother, were not detected when the pups were raised by a control mother. Control pups raised by a foster mother whether gestationally stressed or not had higher levels of NMDA receptors in cortical areas. These findings suggest that the normal expression of DA and Glu receptors is influenced by in utero experience and by lactation. The complex pattern of receptor changes reflects the high vulnerability of DA and Glu systems to variations both in prenatal and in postnatal environment, particularly for cortical D(2) receptors and NMDA receptors in cerebral cortex and nucleus accumbens. In contrast, testis descent appears to be more susceptible to prenatal than to postnatal environmental events.

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