
Research themes
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Julie Carrier
Antonio Zadra
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Pain, sleep and traumatology
In the population, between 10 and 30% of people report chronic pain and
about 2/3 of these patients complain of bad sleep.
Light and the circadian system in humans
Light is not necessary only for vision. Light also has many non-visual
biological functions, which is why controlled light exposure can be used to
treat some mood disorders (like winter depression) and sleep-wake disorders (like
abnormal sleep timing). Conversely, inappropriate timing of light exposure can
have "toxic" effects and be involved in the development of various disorders.
The aim of our NSERC research program is to understand how light is perceived,
interpreted, and used for non-visual functions, especially for the regulation of
our internal biological clock, the circadian system. Contrary to most research
on human subjects in this field, we are studying the effects of light modulated
over the 24-h, instead of the effects of light stimuli, and we combine real-life
field studies with controlled laboratory testing. A first project will focus on
the effects of light exposure at the "wrong" time of day in night workers. The
aim is to identify the characteristics of light exposure that are related to
decreased melatonin production in night workers, because decreased melatonin
production has been associated with increased risks of cancer. A second project
will focus on normal subjects with naturally early or late sleep schedules (the
"chronotypes"). The biological clock of these individuals is adjusted
differently to the external day-night cycle, which makes them an interesting
model to study the role of light in circadian physiology. Since the effects of
light depend not only on light exposure but also on light sensitivity, we plan
to measure both in these subjects. We will develop new methods to measure light
sensitivity, specifically adapted to the assessment of the non-visual system of
light perception. We hope that the results of our studies will contribute to the
development of new prevention and treatment strategies based on controlled light
exposure and manipulations of non-visual light sensitivity.
Sleep and circadian rhythms after moderate and severe traumatic brain
injury
Traumatic brain injury (TBI) is a major public healthcare concern. TBI is the
leading cause of mortality in children and young adults in industrial countries.
TBI can result in short and long-term cognitive, physical, neurobehavioral and
psychological impairments known to interfere with daily living activities and
return to work or school. Chronic sleep-wake disturbances, particularly fatigue,
hypersomnia, and insomnia, are among the most severe, the most persistent and
the most disabling symptoms after TBI. They affect at least 50% of this
population and are present across the range of TBI severity. Despite the high
prevalence of post-traumatic sleep-wake disturbances and their consequences on
quality of life, their emergence and their evolution are still poorly understood.
Our research program proposes to objectively measure sleep and circadian rhythms
in the acute stage after a TBI, to investigate factors contributing to sleep-wake
disturbances and to study the progression of these sleep-wake disturbances over
one year.
Molecules involved in the recovery aspect of sleep
In modern societies, there is a drastic rise of chronic sleep loss, as exemplified by reduced sleep duration in children and adolescents, and increasing prevalence of insomnia and night work. However, the mechanisms underlying its adverse effects on mental health, vigilance, learning, and mood are poorly understood. It is known that sleepiness increases with the duration of wakefulness. Moreover, the longer the duration of wakefulness, the more intense/deep the subsequent sleep. Recent work supports the involvement of synapses, the functional unit of communication between neuronal cells, in this process. Adhesion proteins are elements that bind to other adhesion molecules and are involved in holding the two sides of the synapse together. Importantly, these proteins controls the type of excitatory synapses that predominates in the brain, which type is also linked to both deleterious effects of sleep loss and sleep intensity regulation. In this program currently financed by CIHR and NSERC, the contribution of synaptic adhesion molecules to sleep regulation is investigated. First, markers of sleep intensity (i.e., brain electrical activity and gene expression) are evaluate in mice where specific adhesion molecules are absent or decreased. Second, the effect of the duration of time awake on specific adhesion molecules will be examined by measuring gene and protein expression in the mouse brain after sleep deprivation (i.e., preventing sleep for different durations). Lastly, because we observed that the expression of specific adhesion molecules could be modulated by precise factors driving transcription (i.e., the reading of a gene expressed as a transcript), we will identify the functional DNA sequences within their gene by in vivo (in mice) and in vitro (assays with cells in culture) methodologies. The results of the project will advance our understanding of neuronal functions, and assist in the prevention and in the development of interventions for people suffering from sleep debt accumulation, including age-related disturbances and insomnia.