2023-10-02 11:00:05
Disturbances of sleep and the internal biological clock are frequently associated with neurodegenerative Parkinson’s disease. However, the link between biological rhythm and the process of neuronal degeneration remains uncertain. A team from the University of Geneva (UNIGE) was interested in the destruction of neurons at various times of the day in using the vinegar fly as a study model. Scientists have discovered that the type of cellular stress involved in Parkinson’s disease is more harmful to neurons when it occurs at night. This work can be read in the journal Nature Communications.
More dopamine neurons in the adult Drosophila brain survive in control flies (left) than in circadian mutant flies (right).
© Lou Duret
Parkinson’s disease is a progressive neurodegenerative disease, characterized by the destruction of certain neurons in the brain: dopamine neurons. The main symptoms of this disease are tremors, slowness of movements and muscle stiffness. Epidemiological studies show that other disorders may be associated such as sleep and circadian cycle disturbances.
This cycle, defined by the alternation between periods of wakefulness and sleep, lasts approximately 24 hours and constitutes the internal clock of the human body which regulates almost all of its biological functions. The circadian clock (Described for the first time in 1729 by the mathematician and astronomer…) controls in particular the secretion in end of the day of the “sleep hormone” (melatonin), the variation in body temperature (lower very early in the morning and higher during the day), metabolism during periods of fasting (during sleep) or energy intake (during meals during the day).
Cause or consequence?
Disturbances of this circadian rhythm and sleep can be observed years before the appearance of motor symptoms (A motor is a device transforming non-mechanical energy (wind, chemical, etc.) in affected patients of Parkinson’s disease. But does disruption of the circadian cycle contribute to the development of the disease, or is it a consequence?
This question is at the heart of the work of the laboratory of Emi Nagoshi, associate professor in the Department of Genetics and Evolution of the Faculty of Sciences at UNIGE. His team uses the vinegar fly (or Drosophila) as a study model for Parkinson’s disease and to dissect the mechanisms of dopamine neuron degeneration. Scientists can in fact simulate the onset of the disease by exposing (Exponent can mean:) flies for a few hours to a drug causing oxidative stress which leads to the death of dopaminergic neurons in the following days.
Neurons are more fragile at night in flies
Although they are very different species, the biological clocks of flies and humans are comparable. To determine whether the circadian cycle could exert an influence on the onset of Parkinson’s disease, flies were exposed to oxidative stress at six different times of the day and night.
“We waited seven days to observe the survival of the targeted neurons under a microscope and we observed a greater number of dopaminergic neurons destroyed when the exposure was made during the night hours,” explains Michaëla Dorcikova, former doctoral student at the Department of Genetics and Evolution and first author of the study.
In order to understand whether these observations are dependent on the circadian rhythm, the scientists exposed mutated flies whose circadian cycle was disrupted to the same stresses. The researchers observed that the neurons of flies without an internal clock are more sensitive to oxidative stress. These results thus suggest that the circadian clock exerts a protective effect on dopaminergic neurons against oxidative stress.
Exploring risk factors for Parkinson’s disease
The majority of Parkinson’s cases result from an interaction between multiple genetic risk factors and exposure to environmental factors such as pesticides, solvents and air pollution throughout life. The results obtained show that an oxidative stress factor, such as a pesticide, administered at a specific time of the day can have a critical impact. on the survival of dopaminergic neurons.
“Our results also suggest that genetic variations in circadian clock genes could represent a risk factor for dopaminergic neurodegeneration. We must now ensure the relevance of these results in humans,” concludes Emi. Nagoshi, last author of the study.
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