Neurology Central

Circadian rhythm disturbance could influence Parkinson’s disease onset

New research by a team at Lewis Katz School of Medicine at Temple University (PA, USA) has identified a potential link between Parkinson’s disease and chronic lack of sleep or irregular sleep-wake cycles. The results were published recently in Molecular Psychiatry.

The study, which was led by Domenico Praticò (Lewis Katz School of Medicine at Temple University ) indicates that disturbances to the circadian rhythm that are present prior to the onset of Parkinson’s disease play a part in worsened motor and learning deficits developed as a consequence of the disease. The study is also the first to demonstrate that an environmental factor, in the form of daily exposure to long periods of light and short periods of darkness, can influence the severity of Parkinson’s symptoms.

Many think that sleep disturbances are secondary to Parkinson’s disease,” explained Praticò. “But circadian rhythm disturbances are increasingly reported before the onset of Parkinson’s, suggesting that they could be risk factors.”

Praticò and his team believe that in idiopathic cases of Parkinson’s, which make up the majority of cases in individuals over 60 years of age, the disease arises due to key interactions between genes and environmental risk factors such as stress, sleep disorders and circadian disturbances, all of which have an impact on the functioning of the central nervous system.

The current study focused in on the role of altered circadian rhythm patterns using a mouse model of Parkinson’s disease. Healthy mice were divided into two groups; the control, which were maintained on a regular circadian schedule of 12 hours of light followed by 12 hours of dark, and the treatment group that received 20 hours of light followed by 4 hours of dark. After 60 days, selected mice from each group were treated with MPTP to induce known symptoms and pathology of Parkinson’s disease.

All mice treated with MPTP developed Parkinson’s disease, however those which came from the altered circadian rhythm group exhibited significant learning impairment and severe motor deficits. These motor deficits resulted in reductions in coordination and learning skills far worse than observed in the MPTP-treated mice with normal circadian rhythm.

The team then examined the effects of circadian rhythm disturbance on the brains of the mice. Results indicated significant reductions in neurons that produce dopamine in the substantia nigra which is a key feature of Parkinson’s disease. “Cells normally die in that region of the brain, but our study shows that circadian rhythm disturbance accelerates cell death there,” commented Praticò.

Additionally, microglia within the circadian-disrupted MPTP-treated mice were ‘superactive’, which can increase neuroinflammation.

The researchers now plan to try and replicate the findings in other animal models. “If those studies are successful, we’ll then try to re-establish normal circadian rhythm in circadian-disrupted animals to explore the possibility of reversing brain inflammation and cell death.”

Source: Temple University Hospital press release