Research

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.

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.

Our program, currently financed by CIHR and NSERC, investigates the contribution of synaptic adhesion molecules to sleep regulation. Firstly, markers of sleep intensity (i.e., brain electrical activity and gene expression) are evaluate in mice where specific adhesion molecules are absent or decreased. Secondly, the effect of the duration of time awake on specific adhesion molecules is 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 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 our program 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.

 

Team

Lab Members:

	Chloé Provost Research Assistant, Animal Health Technician Animal Health Technical Studies (Collège Lionel-Groulx)
	Pierre-Olivier Gaudreault, B.Sc. Ph.D. candidate in neuropsychology R/I, Université de Montréal Direction by Dre Nadia Gosselin and Dre Julie Carrier Study of diffusion tensor imaging in patients with severe traumatic brain injury and in the normal aging
	Bong Soo Seok, B.Sc. M.Sc. candidate in Neuroscience, Université de Montréal Effect of the absence of Neurologin-2 on sleep architecture and electroencephalographic activity in mice
	Cassandra Areal, B.Sc. M.Sc. candidate in Neuroscience and MD student, Université de Montréal Co-direction with Nahum Sonenberg (McGill University) Role of translational repressors 4E-BP1 and 4E-BP2 in sleep regulation
	Emma O’Callaghan, Ph.D. Postdoctoral fellow in Neuroscience, Université de Montréal Study of mechanisms underlying the role of Neuroligin-1 in the recovery aspect of sleep
	Lydia Hannou, B.Sc. M.Sc. candidate in Biomedical Sciences, Université de Montréal Study of the transcriptional regulation of Neuroligin-1 by the clock proteins
	Julien Dufort-Gervais, B.Sc. M.Sc. candidate in Pharmacology, Université de Montréal Co-direction by Dr Jonathan Brouillette Impact of Aß oligomers on Neuroligin-1
Previous Lab Members:
	Erika Bélanger-Nelson, M.Sc. Research Coordinator M.Sc. in Neuroscience (McGill University)
	Marlène Freyburger, Ph.D. Ph.D. in Neurological Sciences, Université de Montréal Role of several families of synaptic adhesion molecules in sleep homeostasis and the circadian timing system
	Meriem Sabir, M.Sc. M.Sc. in Biomedical Sciences, Université de Montréal Study of the effect of a mild traumatic brain injury on the sleep structure in a mouse model
	Janine El Helou, M.Sc. M.Sc. in Biomedical Sciences, Université de Montréal Expression of synaptic adhesion proteins as a function of sleep pressure
	Renaud Massart, Ph.D. Postdoctoral fellow (McGill University) Impact of sleep deprivation on the epigenome in the cerebral cortex
	Adeline Rachalski, Ph.D.  Postdoctoral fellow Sleep in primates and murine model of autism

Publications

Areal CC, Warby SC, Mongrain V. Sleep loss and structural plasticity. Curr Opin Neurobiol 2017, 44, 1-7.

O'Callaghan EK, Ballester Roig MN, Mongrain V. Cell adhesion molecules and sleep. Neurosci Res 2016, in press.

Freyburger M, Pierre A, Paquette G, Bélanger-Nelson E, Bedont J, Gaudreault PO, Drolet G, Laforest S, Blackshaw S, Cermakian N, Doucet G, Mongrain V. EphA4 is involved in sleep regulation but not in the electrophysiological response to sleep deprivation. Sleep 2016, 39(3), 613-624.

Bélanger-Nelson E, Freyburger M, Pouliot P, Beaumont E, Lesage F, Mongrain V. Brain hemodynamic response to somatosensory stimulation in Neuroligin-1 knockout mice. Neuroscience 2015, 289, 242-250.

Sabir M, Gaudreault PO, Freyburger M, Massart R, Blanchet-Cohen A, Jaber M, Gosselin N, Mongrain V. Impact of traumatic brain injury on sleep structure, electrocorticographic activity and transcriptome in mice. Brain Behav Immun 2015, 47, 118-130.

Rachalski A, Authier S, Bassett L, Pouliot M, Tremblay G, Mongrain V. Sleep electroencephalographic characteristics of the Cynomolgus monkey measured by telemetry. J Sleep Res 2014, 23(6), 619-627.

Massart R, Freyburger M, Suderman M, Paquet J, El Helou J, Bélanger-Nelson E, Rachalski A, Koumar OC, Carrier J, Szyf M, Mongrain V. The genome-wide landscape of DNA methylation and hydroxymethylation in response to sleep deprivation impacts on synaptic plasticity genes. Transl Psychiatry 2014, 4, e347.

Rachalski A, Freyburger M, Mongrain V. Contribution of transcriptional and translational mechanisms to the recovery aspect of sleep regulation. Ann Med 2014, 46(2), 62-72.

El Helou J, Bélanger-Nelson E, Freyburger M, Dorsaz S, Curie T, La Spada F, Gaudreault PO, Beaumont É, Pouliot P, Lesage F Frank MG, Franken P, Mongrain V. Neuroligin-1 links neuronal activity to sleep-wake regulation. PNAS USA 2013, 110(24), 9974-9979.

Westfall S, Aguilar-Valles A, Mongrain V, Luheshi GN, Cermakian N. Time-dependant effects of localized inflammation on peripheral clock gene expression in rats. PLoS ONE 2013, 8(3), e59808.

Curie T, Mongrain V, Dorsaz S, Mang G, Emmenegger Y, Franken P. Homeostatic and circadian contributions to EEG and molecular state variables of sleep regulation. Sleep 2013, 36(3), 311-323.

Hasan S, Dauvilliers Y, Mongrain V, Franken P, Tafti M. Age-related changes in sleep in inbred mice are genotype dependent. Neurobiol Aging 2012, 33(1), 195.e13-26.

Mongrain V, La Spada F, Curie T, Franken P. Sleep loss reduces the DNA-binding activity of BMAL1, CLOCK and NPAS2 to specific clock genes in the mouse cerebral cortex. PLoS ONE 2011, 6(10), e26622.