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Sleepless nights and the clock gene
7/7/10

The conclusion Christina Schmidt drew was the following: ‘Sleep pressure impacts negatively on the activity levels of the region of the suprachiasmatic nucleus during the vigilance task. We have shown for the first time in human beings – and for the second time for all of the species – that the activity of the cerebral circuits responsible for circadian regulation is modulated by the homeostatic processes of sleep. This suggests that ‘morning subjects’ suffer more strongly than ‘evening subjects’ from the impact of sleep pressure which accumulates over the course of the day, a pressure which obstructs the optimal expression of an alarm signal by the region of the suprachiasmatic nucleus and the locus coeruleus.’

PERIOD 3: a double sided mirror

Another study was carried out by the Cyclotron Research Centre jointly with the University of Surrey’s ‘Surrey Sleep Centre,’ in England.  It was based on individual vulnerability to sleep deprivation and the results were published on June 24, 2009, in The Journal of Neurosciences (2).

Fist of all, the antecedents. Derk-Jan Dijk’s team at the University of Surrey showed in 2007 that one of the circadian clock genes in mammals, PERIOD3 (PER3), intervened in the homoeostatic regulation of sleep. The gene PERIOD3 is equipped with a polymorphism specific to primates characterised by the repetition of the same motif, either four times or five times. There exist homozygotes of the short form (allele) PER34/4 and others of the long form PER35/5.  Better still, English researchers have brought to light the fact that PER35/5 individuals are more sensitive to sleep deprivation than the others (PER34/4). ‘Pretty curiously, the two populations are in no way to be distinguished by their circadian markers,’ specifies Pierre Maquet. ‘This we observe no differences between them in terms of the secretion of melatonin or cortisol, central temperature, the expression of clock genes in the leukocytes, etc. On the other hand it is acknowledged that the ‘5/5s’ accumulate sleep pressure more quickly. The proof is that they produce more slow waves in the first sleep cycles.’

Here it is the genes which have their say, and not individual preferences. Over the course of a normal day, the two groups of individuals (4/4 and 5/5) maintain a relatively stable and equivalent level of cognitive performances. Nonetheless, after sleep deprivation the individuals who are more vulnerable because of their genetic membership will at the end of the evening end up facing a more pronounced worsening of their performances than the less vulnerable people, those endowed with allele 4/4 of the PER3 gene.

But what is going on in concrete terms in the brains of the two groups? This is what Pierre Maquet and his colleagues wanted to discover through functional magnetic resonance imaging (fMRI). They built up a group of 15 PER34/4 subjects and another of 13 PER35/5 subjects on the basis of strict criteria – aged between 18 and 30 years, being right handed, not complaining of any sleep problems, having no traumatic or psychiatric medical history, not consuming coffee or alcohol to excess, not having made a journey over the previous two months which went beyond one time zone, not having a body mass index greater than 27, not consuming psychoactive medicines or drugs, and not having been part of a night work team in the last year. Furthermore the two sample groups were similar in terms of age and gender, as well as of temperament, in terms of anxiety levels, intelligence quotient and the educational levels of their members.

The experiment protocol was based on an executive task: the 3-back task. The participants heard a letter being said every 2.5 seconds and they had to determine if it was the same one which had been said out loud 7.5 seconds previously. For example: H M O P – no, H M O H – yes. ‘This task demands considerable mental effort,’ stresses Pierre Maquet. ‘We chose it because the studies carried out at the University of Surrey had taught us that performances for this test worsened for 5/5 subjects after sleep deprivation whilst this wasn’t the case for the 4/4 subjects.’ The challenge was put to the participants in the morning (either 1h30 or 25h after waking) and in the evening (after 14h of continual wakefulness), once after a night of sleep and another after a night’s sleep deprivation. The subjects’ cerebral activity was measured by fMRI.


(2)    Gilles Vandewalle, Simon N. Archer, Catherine Wuillaume, Évelyne Balteau, Christian Degueldre, André Luxen, Pierre Maquet et Derk-Jan Dijk, Functional Magnetic Resonance Imaging-Assessed Brain Responses during an Executive Task Depend on Interaction of Sleep Homeostasis, Circadian Phase, and PER3 Genotype, in The Journal of Neuroscience, 24 juin 2009 – 29(25):7948-7956.

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