MARCH
APRIL 2017
#35
THE MAGAZINE OF THE FRENCH NATIONAL
INSTITUTE OF HEALTH AND MEDICAL RESEARCH
Sleep
Health and
Sleep
#35
EDITORIAL
Lack of sleep:
watch out!
©
ouen
nne Beg
/Ètie
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The alarm has been raised for more than ten years, but things
are getting worse. We of the modern world do not get enough
Adrien
Joëlle
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tus Directo
gist, Emeri ôtel-Dieu
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,
h at Inserm
sof Researc P) - Université Pari
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In
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e
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in
ent of th la
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s
ré
P
,
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e
de
Descart
sommeil et
national du ational Institute
vigilance (N & Vigilance)
of Sleep
sleep. Both young and old, we demote sleeping to the bottom of our
priorities. Not just below performance and work but even behind leisure activities. Consciously or not, we ignore the—often serious—consequences of insufficient sleep on our mental and physical faculties,
and on our health. A real public health problem, lack of sleep is
also a social issue because in an era of new information and communication technologies, we are living a round-the-clock life seven
days a week. The result is that we do not set aside either enough
time or space free of external stimulation, an essential condition
for "good" sleep. A hyperconnected civilization with a social life
that encroaches deep into the night, putting off the time we go
to bed but not the time our alarm clock goes off. Furthermore,
the virtues of getting up early are extolled, but less emphasis
is put on the corollary fact that this means going to bed earlier
in order to ensure enough sleep. Finally, the focus on "well-being"—another performance contest—is intensified by the world of
connected objects and their manifold applications. It is important to
point out that none of these are capable of analyzing sleep—contrary
to what their designers claim. Given this proviso, they can be of use
when it comes to recoding physical activity and daily rhythms, thus
providing information about the effects of daily habits on sleep and
therefore, the impact of this important factor on health.
Director of Publication Yves Lévy Director of Writing Arnaud Benedetti Chief Editor Yann Cornillier Writing Assistants Coralie Baud,
#35
March - April 2017
Subscription free, write to:
[email protected]
Inserm, 101, rue de Tolbiac
75654 Paris Cedex 13
www.inserm.fr
Marie-Charlotte Ferran Headlines Julie Coquart Editorial Assistant Coralie Baud Collaborators on this issue: Kheira Bettayeb, Alice
Bomboy, Françoise Dupuy Maury, Jean Fauquet, Alexandra Foissac, Stéphany Mocquery, Pascal Nguyên, Agnès Noël, Julie Paysant, Hélène
Perrin, Simon Pierrefixe, Vincent Richeux, Nicolas Rigaud, Angeline Rouers, Bruno ScalaGraphic Design Primo&Primo Art Direction Myriem
Belkacem, Primo&Primo Symbols Cécile Depot Cover Credits Illustration: Amélie Barnathan Printer Aubin Imprimeur
ISSN No.: 2119-9051 Legal submission: March 2017
This product is 100% recycled.
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#35
#35
Close-Up
SLEEP
Health and
Sleep
piled by
Report com nt
Vince
x
Richeu
We spend one third of our lives asleep. Sleep appears to be essential for proper
physical recovery. Recent findings also demonstrated that it is an essential part
of the learning process. But what happens inside our brains after we fall asleep?
The 17th National Sleep Day organized on 17 March 2017 by the Institut national
du sommeil et de la vigilance (INSV, National Institute of Sleep & Vigilance) gave
Science&Santé the chance to learn about the latest discoveries that are steadily
lifting the veil on the roles of different types of sleep, be it light, deep or rapid eye
movement sleep. An opportunity to understand the repercussions—both shortterm and long-term—of poor sleep on our health.
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#35
O
n at least one point, the picture is reassuring: the average
time spent sleeping by French
people has stabilized. After a long, apparently inexorable decline, it seems to
have now bottomed out at an average
of 7 h 05 during the week and 8 h 10 at
the weekend, according to a 2016 survey conducted by the Institut national
du sommeil et de la vigilance (INSV,
National Institute of Sleep & Vigilance)
on a representative sample of the active
French population. These figures have
changed little over the last five years
and are now within the normal range
in developed countries. Nevertheless,
in just half a century, the time devoted
to sleep every night has decreased by
one-and-a-half hours. And annual INSV
polls only confirm that the French do
not sleep enough.
"Most adults need to sleep for at least
eight hours a night. Although needs vary
from one person to another, it isn't the
time itself that indicated the need for
longer sleep but rather the difference
between week days and weekends", explains Joëlle Adrien, President of INSV.
"Surveys have shown that, globally, the
French do not sleep enough given that
they need an extra hour at the weekend
to catch up." And for many people, sleep
debt is a particular problem. One in four
French people claim they sleep less than
six hours a night on work days, a deficit
that results in their sleeping an hourand-a-half or even two hours longer at
the weekend. "However, sleep debt cannot always be caught up in two nights
and can build up over time", explains
the neurobiologist. "It is estimated that
one-third of the French population suffers from chronic sleep debt." The effects of acute sleep deprivation are well
characterized, and notably include poor
concentration, impaired performance,
drowsiness and irritability. According
to Joëlle Adrien, "if someone who needs
between 6 h 30 and 8 h 30 of sleep only
gets 6 hours for five days straight, the
Joëlle Adrien: Emeritus Director of Research at Inserm, HôtelDieu de Paris (AP-HP) - Université Paris-Descartes
2INSV/MGEN 2016 Survey, Sleep and New Technologies
grand angle
repercussions on performance are the
same as those of missing a whole night's
sleep." The long-term consequences of
sleep deprivation can be far more serious, including psychiatric problems and
learning difficulties. And recent studies
have suggested that other consequences
may include higher risks of cardiovascular disease, obesity and diabetes, inflammatory disease and even cancer.
Ninety-minute cycles
Why such repercussions? To understand,
we first need to look at the different
types of sleep, a complex pattern that
varies not only from one individual to
another but also with age. In all mammals including humans, this activity—
or inactivity—to which we dedicate a
third of our lives, is composed of different phases which are referred to as
light, deep or slow-wave and rapid eye
movement (REM) sleep. "These phases
follow one another to constitute a cycle
which on average lasts ninety minutes in
adults, although this can vary between
sixty and one-hundred-and-twenty
minutes", explains the sleep specialist. "In normal conditions, a night's
sleep consists of three to five successive cycles." Once you fall asleep, the
light sleep phase occurs within a few
minutes. Brain activity slows down, but
Good sleep:
the rules
How to sleep better Tips from
the Institut national du sommeil
et de la vigilance (INSV, National
Institute of Sleep & Vigilance):
adopt regular sleeping habits.
Go to bed and get up at the
same times to help synchronize
your waking/sleeping rhythm;
expose yourself to sunlight. To
work properly, your internal
clock needs to be stimulated
by natural light;
do physical activity regularly
but not after 8 p.m. In the evening, falling asleep is easier and
the quality of sleep is better;
avoid stimulants (tea, coffee,
Vitamin C) after 3 p.m.; similarly, smoking and drinking in
the evening are both associated with nighttime waking;
keep the evening meal light
and finish it at least two hours
before going to bed; favor
foodstuffs rich in slow carbohydrate (potatoes, rice, bread,
pasta). These make for stable
sleep by providing a constant
energy supply throughout the
night.
keep the temperature in the
bedroom around 18°C. Low
body temperature is a trigger
factor for going to sleep so it
www.institut-sommeil-vigilance.org
is better not to over-heat the
bedroom;
make the room completely dark at bedtime. Melatonin is secreted in the absence
of light stimulation and triggers sleep.
•
•
•
•
•
•
•
©©INSV/Shutterstock
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Sleep
Awake
Stage 1
REM sleep
Stage 2 Stage 3
Electroencephalography traces
corresponding to the awake state
and different phases of sleep
Percentage of
sleep time
Awake
20-25 %
REM sleep
4-5 %
Light slow-wave sleep
45-55%
Deep slow-wave sleep
16-20 %
Time after falling asleep
As the night progresses, restorative
deep slow-wave sleep gives way to
light slow-wave sleep.
0h
1h
2h
3h
4h
5h
6h
7h
k
©©Inserm/Alexandra Pinci
Stage 1 Passage from waking to sleeping
waking up is still easy. After some 15-30
minutes, deep sleep sets in. This is when
brain activity is at its lowest and it is
in this phase that the body can really
recover. The liver stores glucose and tissues regenerate under the influence of
the growth hormone which is most active at this time. After about an hour of
deep, slow-wave sleep, the first episode
of REM sleep begins. "From its inactivity, the brain starts to function much
faster, almost reaching the level of activity seen when awake. However, muscle
tone—which is maintained during slowwave sleep—completely disappears",
says Joëlle Adrien. It is as if the body is
paralyzed except for the face where the
eyes move about rapidly, hence the term
REM sleep. (Another term is paradoxical sleep which derives from the fact that
this phase is characterized by fast brain
activity.) Although the exact function of
short, it becomes longer in subsequent
this phase is poorly understood, it seems
cycles, reaching 45 minutes by the end
to be particularly important for physiof the night. "With deep sleep accountcal and nervous system recovery. After
ing for nearly half of the early cycles,
10-20 minutes, the sleeper goes into a
the first three or four hours of sleep are
new cycle of slow-wave
key to the body's physical recovery", emphaand REM sleep and such
sizes Joëlle Adrien. “In
cycles succeed through"In
REM
sleep,
out the night. If nothing
the second half of the
happens to interrupt the
night, light slow-wave
the brain starts to
night's sleep, the sleeper
sleep takes over which is
will wake up spontane- function much faster, why it is easier to wake
ously once he or she has
almost reaching the up during this stage. A
gone through enough
good night's sleep therelevel of activity seen fore depends not only
cycles.
on quantity (enough)
As the night progresses,
when awake"
but also quality, with
the composition of the
the right proportions of
cycles changes. While
light slow-wave sleep
deep slow-wave sleep
and REM sleep." "Enough" means
predominates in the early nighttime,
knowing how much you need and adaptit gives way to lighter slow-wave sleep
ing your lifestyle accordingly. Age is also
in the early morning hours. In parallel,
a factor in this calculation, as the need
while the first REM phase is relatively
7
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#35
grand angle
for sleep changes as we get older. Prepubescent children spend a long time in
deep slow-wave sleep but the proportion
drops down to 20-25% in adulthood,
and then just 5-10% after the age of
80. Sleep at that age is lighter and more
sensitive to environmental stimuli. As
a result, sleep becomes less restorative
with age as less time is spent in the deep
slow-wave phase and nighttime waking is more frequent. In parallel, REM
sleep takes up far more time in young
childhood, accounting for some 80% of
a new-born's sleeping time. By the end
of adolescence, this has dropped down
to 20-25% and stays fairly constant
through adulthood.
SLOW-WAVE SLEEP
REM SLEEP
In REM sleep (bottom), the brain is
more active (red areas) than in slow-wave
sleep (top). Images generated by positron
emission tomography, a technique that
measures an organ's metabolic activity.
k
To switch from a waking state to sleep
and get the most from this vital rest
phase, tiredness alone is not enough.
There is also the question of circadian
rhythm and the internal clock. And here,
we differ enormously. Body temperature, blood pressure, the production of
hormones (like growth hormone), cognitive function, mood—almost all the
body's physiological functions are governed by a circadian rhythm, locked into
a 24-hour cycle. And it is our internal
clock that sets this rhythm. The internal
clock is located in the hypothalamus,
a structure deep inside the brain that
consists of some 20,000 neurons. Under
the influence of about fifteen "clock"
genes, it beats out a rhythm of between
23 h 30 and 24 h 30, depending on the
individual. This feature of the internal
clock explains why everyone has their
k
A section through mouse
retina. In the inner layer, a
melanopsin retinal ganglion
cell (which is connected to the
brain's internal clock).
©©Hank Morgan /SPL/Phanie
Synchronization of the
internal clock
own genetically determined rhythm, or
more accurately chronotype, which dictates whether you go to sleep earlier or
later. To lock the cycle into the 24-hour
day, exposure to light is key. "Without
light stimulation, we would go to sleep
either earlier or later every day. The
light-dark cycle is necessary for correct
synchronization of the biological clock
and, in consequence, high quality sleep",
explains Claude Gronfier, neurobiologist
at the Institut cellule souche et cerveau
(Stem Cell and Brain Research Institute)
in Lyon and Vice-President of the Société
francophone de chronobiologie (Frenchspeaking Society of Chronobiology).
"Daylight stimulation involves special
photosensitive cells in the eye's retina
called melanopsin retinal ganglion
cells3 which were discovered in 2002.
These are connected to the suprachiasmatic nuclei in the hypothalamus (where
the internal clock is located) which are
in turn connected to other structures in
the brain that control the body's various functions." Light also stimulates the
pineal gland, a small gland behind the
hypothalamus which secretes melatonin.
Melatonin production is initiated at the
end of the day and this hormone contributes to the process of falling asleep.
We are just beginning to understand
more about this process of falling asleep.
For a long time, scientists believed that
passing from the waking state to sleep
involved changes in electrical activity,
generated at the same time in all the
brain's various structures. As if it were
controlled by a single, central switch.
But this picture has been changed as a
result of investigations in epileptic patients being prepared for surgery. For
a long time, brain activity could only
be measured via electrodes placed on
the outer skull. But now, electrodes can
be inserted into the brains of epileptic
patients in order to locate the foci of
their seizures, which has given scientists
access to new data. Using these electrophysiological recordings, Hélène Bastuji
Claude Gronfier: Inserm Unit 1208/Inra – Université Claude-
©©Inserm/ Howard Cooper
Bernard Lyon 1, Chronobiology & Emotional Disorders
Hélène Bastuji: Inserm Unit 1028/CNRS/Université Jean-Monnet
Saint-Étienne - Université Claude-Bernard Lyon 1
4Melanopsin. Light-sensitive pigment found in certain
photoreceptive cells in the retina that are involved in non-visual
responses to light
#35
2. Visual system 1 in sleep
(2) become distinct and communicate less with the primary visual regions
(3) than when awake (1).
©©Habib Benali
k
Functional MRI images showing information exchanges in the part of the
brain that controls the visual system. While asleep, exchanges are more
localized (as in all the other cerebral networks): associative visual regions
3. Visual system 2 in sleep
©©Consecte tempor incidunt ut labore
1. Visual system during waking
9
slow-wave sleep. They get volunteers
fallen sleep, enough parts of the brain
and her team at the Centre de recherche en neurosciences
to fall asleep in a functional Magnetic
must have switched into
(Neuroscience Research "To get the impression slow-wave sleep, but not
Resonance Imaging (fMRI) machine and
Center) in Lyon have
directly measure their brain activity from
necessarily all of them." been able to study the of having fallen sleep, I n t h e B i o m e d i c a l
when they fall asleep until they wake up.
"We have been able to map interactions
various waves (that
Imaging Laboratory
enough parts of
between different parts of the brain to
translate neuron actiat La Pitié-Salpêtrière
the brain must have H o s p i t a l i n P a r i s , investigate how information is being
vation) running through
Habib Benali and his
the brain between wakprocessed. Compared with the waking
switched into slow- colleagues
ing and sleeping. Two
focus on
state, processing was more localized
structures—that work
changes in how different
during the deep and REM phases of
wave sleep"
synchronously in the
parts of the brain intersleep. Interactions there are no longer
act in sleep, in particular during deep
waking state—drew their attention:
global but are confined to regions that
the thalamus in the middle of the brain
and the cerebral cortex, the brain's
outermost layer of neural tissue. "We
Traces showing time-to falling asleep in
observed that changes in brain activity
different parts of the cortex (highlighted on B) and
associated with falling asleep, notably
the thalamus (red trace).
the switch to slow waves, happen first
in the thalamus, up to twenty minutes
before they occur n the cerebral cortex",
explains Hélène Bastuji. The cortex is
the center of consciousness and the fact
that it "falls asleep" later could account
for the hallucinations and floating sensations so common when dropping
off. "To get the impression of having
k
2M. Magnin et al. PNAS, 23 February 2010,
doi: 10.1073/pnas.0909710107
2M. Boly et al. PNAS, 10 April 2012,
doi: 10.1073/pnas.1111133109
©©Michel Magnin
Habib Benali: Inserm Unit 1146/CNRS – Université Pierre-etMarie-Curie, Biomedical Imaging Laboratory (on secondment at Concordia)
grand angle
#35
Parts of the brain
involved in
sleep
Thalamus
By curtailing its activity
before the cerebral cortex,
it inhibits stimulation via sensory
pathways and makes it easier
to fall asleep.
Hippocampus
Involved in the consolidation
of memories. It sorts information
and, during sleep, relays it to
the cortex for long-term
registration.
Pons cerebelli
Blocks the brain stem when
passing into REM sleep to
induce relaxation of the muscles.
It prevents bodily activity when dreaming.
Hypothalamus
Amygdala
Involved in emotions—that
are very active when dreaming.
©©Inserm/Alexandra Pinci
Controls the onset of sleep.
The location of the biological
clock that is conditioned
by the dark-light cycle and
is important in falling asleep.
Reticular formation
Controls passage from waking
to sleeping. It sets the general
level of central nervous system activity.
are closer together", notes Habib Benali.
The scientists interpret these exchanges
between sub-structures during sleep as a
sign of the organizing and integration of
information gathered during the day as
part of the memorization process. "All
phases of sleep seem to be involved in
transferring and consolidating the day's
information but we do not yet know at
which level." Although the respective roles of the
different phases largely remain a mystery, it is now undeniable that sleep
is indispensable to memorization and
learning. "Slow-wave sleep, especially
the deepest type, is particularly important for declarative memory—that of
knowledge and facts that we are aware
of and remember. REM sleep, on the
other hand, appears crucial for procedural memory—that which records procedures and underlies the "know-how"
required to accomplish tasks", explains
Joëlle Adrien. During sleep, neural circuits used during the day get reactivated
"probably to reinforce assimilation",
adds the neurobiologist. In REM sleep,
during which the brain is nearly as active as it is in waking, this sub-conscious
repetition is accompanied by disconnection from the brain stem, which explains
the muscle relaxation that characterizes
REM sleep. A mechanism that ensures,
like a safety rail, that movement is restricted and our nights—as well as those
of our partners—are uninterrupted and
calm.
Research—using functional MRI in
particular—has confirmed that neurons
stimulated during the day get reactivated
in each phase of sleep. But to different
extents, suggesting that distinct—pre-
Get rid of screens
Exposure to the light from screens of computers, televisions and tablets has one
niggling disadvantage: it delays sleep. Why? The LEDs in these screens emit a
high proportion of blue light to which melanopsin retinal ganglion cells are very
sensitive. And these photoreceptor cells play a central role in synchronizing
the biological clock and regulating sleep. Even brief exposure to a
screen at the beginning of the night
can reset the biological clock so
that it can no longer ensure a person falls asleep quickly, a necessary
prerequisite to restorative sleep.
“Not to mention that the most intensive users of screens, like teenagers, tend to get less exposure to
natural light which is by far the best
way of synchronizing the biological
clock", adds Claude Gronfier. To
avoid a lag, exposure to screens
should be avoided in the two hours
before going to bed. Studies in
children and teenagers have shown
that respecting this interval extends
the night's sleep by an average of
an hour-and-a-half.
2INSV/MGEN Survey 2016, Sleep and New Technologies
©©Fermariello/SPL/Phanie
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#35
Bring back naps!
If you are feeling drowsy, taking a
nap of less than 30 minutes in the
early afternoon will help you stay
alert for the rest of the day. A 10-20
minute nap has the advantage of
restoring concentration and energy
without encroaching on accumulation of the night's "sleep capital". A
longer nap with entry into deep sleep
is more difficult to wake up from and
may interfere with falling asleep that
night. "After lunch, a 20-minutes nap
can reduce the risk of accidents at
work or on the road, enhance memory, foster creativity, relieve stress
and rebalance the nervous system
as well as being good for the digestion and the heart", recommends
the Institut national de prévention
et d’éducation pour la santé (INPES,
National Institute for Health Prevention & Education) in its guide Sleep
Well, Live Better.
Available to download at:
inpes-santepubliquefrance.fr
©©Smokovski/Fotolia
jects. The next day, one of the objects
was moved. The animals were able to
identify it if they had spent 20 minutes
in the chamber the day before but not
The hippocampus: the
if they had only been kept in there for
memory "conductor"
three minutes. “Recordings made while
The importance of slow-wave sleep is
the rats were asleep, just after exposure
now well established in consolidating
to the objects, showed that there was
declarative memories. And the hipmuch more communication between
pocampus, a small cerebral structure
cortex and hippocampus in animals
located underneath the anterior hypowhich had spent a longer time with the
thalamus, is fundamental to this proobjects, and they remembered their posicess. Michaël Zugaro and his group at
tion the following day." To establish a
the Paris Centre interdisciplinaire de
link between this exchange and consolidation of the memory,
recherche en biologie (Interdisciplinary
the scientists wanted
"During slow-wave
Center for Biology
to reinforce coupling
Research) have shown
between the hipposleep, neurons in
campus and the corthat stabilization of
the hippocampus
tex which they did by
memories requires
implanting three innocturnal dialog bespontaneously
tween the hippocamtracerebral electrodes
reproduce the activity into rats which had
pus and the cerebral
cortex. "The role of
only spent three minthey went through
utes with the objects.
the hippocampus in
memorization was
over the waking hours The next day, all these
rats were easily able
revealed in the late
about once every two to identify the object
1950s by a study on
that had been moved!
an epileptic in whom
seconds"
"This experiment was
this structure had
the first to show that
had to be ablated",
hippocampo-cortical coupling mediates
explains the scientist. "His capacity to
memory consolidation during sleep",
form new memories was profoundly
notes Michaël Zugaro. It also shows
compromised". His long-term memories, however, were preserved. On the
that the memorization process can be
basis of these observations, a hypothesis
reinforced by electrical stimulation.
was proposed: while the hippocampus
Before it helps to fix memories on a
is essential for the formation of new
long-term basis, the hippocampus has
memories, long-term memories are held
an astounding capacity for sorting
in the cortex. And hence, dialog between
information registered over the day,
these two parts of the brain are key
storing what is worth keeping and getting rid of what is not. This is what
when it comes to stabilizing memories.
Géraldine Rauchs and her colleagues
By recording activity in the hippocampus and cortex during sleep, scientists
at the Neuropsychology Laboratory in
were able to establish a correlation beCaen have shown, having also focused
tween the activities observed in each of
on this structure's role during sleep. In
these structures. "During slow-wave
an experiment conducted on humans,
sleep, neurons in the hippocampus
the scientists rapidly presented words
spontaneously reproduce the activity
to volunteers with an instruction either
they went through over the waking
hours about once every two seconds.
The cortex then seems to respond with
Michaël Zugaro: Inserm Unit 1050/CNRS – Collège de France
specific brain waves", explains Michaël
Géraldine Rauchs: Inserm Unit 1077/EPHE – UniversitéZugaro. To investigate the link between
Caen-Normandie, Memory & Amnesia
these interactions and memory, the sci2N. Maingret et al. Nature Neuroscience, July 2016,
entists conducted an experiment on
doi: 10.1038/nn.4304
rats that they placed in a rectangular
2G. Rauchs et al. Journal of Neuroscience, 16 February 2011,
chamber containing two identical obdoi: 10.1523/JNEUROSCI.3972-10.2011
sumably complementary—mechanisms
participate in the memorization process.
to "Remember" or "Forget". Half of
the subjects were then allowed a normal
night's sleep whereas the other half were
kept awake. Three days later, their memories were tested. The sleep-deprived
subjects retrieved just as many of the
"Remember" words as those who had
slept normally, but they remembered
more of the words they were supposed
to have forgotten, suggesting that their
brains had failed to correctly suppress
information. Functional MRI examination of the volunteers' brain activity
during memorization showed that the
"Remember" words induced more hippocampal activity (see figure on the next
page). "This part of the brain acts as a
sort of "Table of Contents". During the
day, during the declarative memorization
process, specific populations of neurons
are activated in response to the learning
grand angle
#35
y=-22
Results of a memory
experiment: the parts
of the brain that are
activated to a greater
extent by "Remember"
words than "Forget"
words light up in green in
both groups. In subjects
who have slept well,
the hippocampus (red)
is activated to a greater
extent by "Forget" words
than "Remember" words
compared with those who
are sleep-deprived.
©©Inserm/Université de Liège
command. These labeled neurons then
get reactivated during sleep, the degree
of reactivation being dependent on the
importance of the information. This is
the first step in memory consolidation.",
says Géraldine Rauchs. "Connections
between different parts of the brain during the day in the course of learning get
reactivated during the night by the hippocampus", which therefore takes on
the role of a conductor.
The importance of a good night's sleep
for the consolidation of memories led
to questions about possible links between insomnia and the development
of degenerative disease at advanced age.
By means of imaging examinations in
patients with Alzheimer's disease,
Géraldine Rauchs has also established
a correlation between difficulty falling
asleep and abnormal build-up of betaamyloid peptide in the prefrontal cortex
in the anterior brain. This peptide occurs
naturally in the brain, but its excessive
accumulation is characteristic of neurodegenerative disease. Moreover, in people who complained of frequent waking
during the night, the insular cortex was
atrophic; this lateral part of the cerebral
cortex is involved in generating certain
types of wave during sleep as well as
in the control of certain cognitive functions. The scientists' aim now is to get
a better understanding of sleep patterns
in these people with a view to identifying markers to predict the likelihood of
developing neurodegenerative disease.
"These findings support the idea that
sleep might also have a role in cleaning the brain by getting rid of metabolic
waste. If sleep is perturbed, drainage
via cerebrospinal fluid and exchanges
across the blood-brain barrier might be
k
12
compromised, leading to build-up of
toxic waste inside the brain", suggests
Géraldine Rauchs. "Addressing insomnia in an elderly subject might consequently be a way of slowing cognitive
decline." sleep apnea and its repercussions on the
cardiovascular and metabolic systems.
Sleep apnea syndrome (SAS), which affects 5-20% of the population, is characterized by closure of
the pharynx—complete
"Connections
(apnea) or partial (hySleep apnea
popnea)— several times
between different
While a quantitatively
an hour while asleep.
inadequate amount
This causes various adparts of the brain
verse effects in the body,
of sleep compromises
during the day in the including intermittent
the process of memorization, poor quality course of learning get hypoxia3 in the tissues,
sleep seems similarly
short interruptions of
reactivated during
to have adverse physisleep and major respiological repercussions.
ratory effort. Repeated
the night by the
At the HP2 Hypoxiaepisodes of asphyxia—
Cardiovascular
of which the sleeper is
hippocampus"
and Respiratory
usually unaware—cause
Physiopathology
snoring, morning tiredness, headache, drowsiness and irritabilLaboratory in Grenoble, Jean-Louis
Pépin and his colleagues are looking at
ity. "With episodes of hypoxia, blood
pressure is kept high during the sleeping
hours whereas it should drop in paralCorrelation between
lel to the drop in heart rate so that the
the mean time-to
cardiovascular system can relax and
repair itself", emphasizes Jean-Louis
falling asleep over last
Pépin. "We can therefore assume that
five years and build-up
intermittent hypoxia acts on blood presof beta-amyloid peptide
sure by activating the relevant part of the
in the prefrontal cortex
©©Pierre Branger and Géraldine Rauchs
k
of 51 elderly subjects
with normal cognitive
function
4Hypoxia. Reduced oxygen supply to the tissues
Jean-Louis Pépin: Inserm Unit 1042/Université Grenoble
Alpes
2P. Branger et al. Neurobiology of Aging, May 2016, doi: 10.1016/j.
neurobiolaging.2016.02.009
#35
©©HP2 Laboratory
diovascular system, sufficient sleep of
good quality is vital if the results of
prospective studies are to be believed.
In fact, sleeping less than six hours a
night is a cardiovascular risk factor in
its own right in the context, yet again,
of sleep debt. Analysis of the Canadian
Nurses’ Health Study cohort of 72,000
American nurses followed for ten years
showed that women who slept five hours
or less a night had a 45% higher risk of
coronary artery damage3 in the long
term, compared with those who slept
eight hours a night.
In the same cohort, the risk of type 2 diabetes in women who found it difficult to
fall asleep was 39% higher. It thus seems
to be becoming ever more obvious that
insomnia can also cause metabolic prob-
4Atheroma. Progressive thickening of the arterial wall due to
the deposition of fatty plaques
4Cytokine. Cell mediation molecule synthesized by immune
system cells
4Oxidative stress. Imbalance between the organism's
production of harmful oxidative agents (particularly free radicals)
and antioxidants such as vitamins E and C). Induces inflammation
and causes mutation of the DNA.
4Hepatic steatopathy. Liver disease characterized by lesions
due to excess fat
2J. Aron-Wisnewsky et al. Journal of Hepatology, January 2012,
doi: 10.1016/j.jhep.2011.04.022.
2C. Arnaud et al. American Journal of Respiratory and Critical Care
Medicine, 15 September 2011, doi: 10.1164/rccm.201012-2033OC
©©Burger/Phanie
k Treating sleep apnea and snoring with a
Continuous Positive Pressure (CPP) device
In the blood of volunteers subjected to
intermittent hypoxia in a "hypoxia tent"
(bottom), oxygen tension significantly fluctuates
and is lower than when they are in normal air
(top).
k
sympathetic nervous system." The consequences of SAS-related hypoxia have
been probed in the laboratory, initially
in animal subjects. "We showed that
mice experiencing intermittent hypoxia
over eight hours a day for a few weeks
underwent vascular remodeling and accelerated deposition of atheromatous
plaque3, a major risk factor for myocardial infarction. Inflammation was also
observed in adipose tissue, which can
lead to the development of insulin resistance and cardiovascular disease." The
research team then confirmed these results in humans by subjecting a group
of young adults to intermittent hypoxia
in a special "tent" over 14 nights in a
row. At the end of the period, the volunteers who had been healthy at the beginning saw their blood pressure rise.
This was accompanied by activation of
the sympathetic nervous system which
controls the body's sub-conscious activities like heart rate and is also intimately
involved in vascular and cardiac remodeling. As in the animals, the scientists
observed inflammation of adipose
tissue and production of pro-inflammatory cytokines3, both of which can
exacerbate insulin resistance and in
consequence lead to the development
of diabetes. This work is ongoing to elucidate the mechanisms at play, notably
by exposing cultured cells to variable
oxygen tension. "Intermittent hypoxia
due to repeated episodes of apnea induces oxidative stress3 in the tissues.
This can lead to inflammation, insulin
resistance, hardening of the arteries
and hepatic steatopathy3", explains
Jean-Louis Pépin. To preserve the car-
13
grand angle
Lack of sleep stimulates
appetite and a desire for fatty food.
most susceptible. According to a metaanalysis, the risk of overweight and
obesity is two-fold higher in children
and teenagers who do not sleep much.
In order to see if the reverse is true, i.e.
if improving sleep can affect eating habits, Karine Spiegel and her colleagues
recently conducted an experiment in
young overweight and obese subjects
who sleep less than seven hours a night.
They were subjected to two one-week
experimental sequences in random
order. In one, volunteers slept as they
did normally. In the other, they slept
for at least one extra hour each night.
The results (in press) show that during
the week of prolonged sleep, volunteers
were less tempted by fatty and sweet
food, and snacks. Offered an all-youcan-eat buffet at the end of the study,
they showed themselves far more restrained than they had been after the
week in which they had maintained their
habitual pattern of sleep.
Phase shifts
Finally, research is tending to confirm
that sleep is important in immunity. "This
link has not been extensively studied.
One of the most interesting experiments
showed that sleep-deprived subjects are
more likely to contract influenza after
injection of the virus than people who
Orexin receptors (red) on
nerve cells (green). Appetite
is increased when they are
stimulated by insufficient
sleep.
k
hormone that acts in the opposite way
lems. This has been confirmed in a metaand stimulates hunger. "These endoanalysis carried out by an Italian group,
crine changes were associated with
covering 45 studies and a total of more
increased appetite, especially for sweet
than 600,000 subjects. Less than six
and fatty foodstuffs." The scientists
hours of sleep a night raised the risk of
also suspect that orexin—
type 2 diabetes by a factor
a neurotransmitter that
of 28%. "Sleep deprivation
"Sleep
stimulates both hunger and
impairs the regulation of
wakefulness—might be afcarbohydrate metabolism.
deprivation
fected. "Sleep deprivation
It also affects neuro-endocrine function, especially
is accompanied by stimuimpairs the
lation of orexin neurons
the system responsible
regulation of
which would be expected
for telling the brain about
to induce increased dietary
energy needs", explains
carbohydrate
Karine Spiegel from
intake as a result of pleametabolism"
sure due to stimulation of
the Lyon Neuroscience
the brain's dopaminergic
Research Center, who has
systems involved in the reconducted experiments to
ward pathway. This would explain the
investigate the underlying mechanisms.
desire for particularly energy-rich foodIn one of these experiments, 12 young
stuffs." The youngest subjects were the
adults were subjected to two sessions—
one with two nights lasting 4 hours and
the other with two 10-hour nights—in
random order. After sleep deprivation,
there was an 18% drop in the blood
concentration of leptin, a hormone that
tells the brain about satiety; in parallel, there was a 28% rise in ghrelin, a
©©Fotolia
#35
k
Karine Spiegel: Inserm Unit 1208/Inra – Université ClaudeBernard Lyon 1, Waking - Integrated Physiology of the Waking System
4Coronary artery. Artery that supplies heart muscle.
2NT. Ayas et al. Archive of Internal Medicine, 27 January 2003,
doi: 10.1001/archinte.163.2.205
2Y. Li et al. Diabetologia, April 2016,
doi: 10.1007/s00125-015-3860-9
2FP. Cappuccio et al. Diabetes Care, February 2010,
doi: 10.2337/dc09-1124
2K. Spiegel et al. Lancet, 23 October 1999,
doi: 10.1016/S0140-6736(99)01376-8
2K. Spiegel et al. Annals of Internal Medicine, 7 December 2004;
141(11): 846-50
2Y. Fatima et al. Obesity Reviews, February 2015,
doi: 10.1111/obr.12245
©©C-JGuérin /SPL/Phanie
14
#35
k Night-shift
work—largely
confined to the
tertiary sector—
interferes with
biological rhythms
causing a vicious
cycle of adverse
health impacts.
Research Center) in Lyon has classified
night-shift work as "probably carcinogenic". The Cecile Cohort that included
women working exclusively at night revealed that their risk of breast cancer
was 30% higher. "Although, broadly
speaking, sleep problems are being better dealt with in general medicine, this is
not so for problems affecting circadian
rhythm", says Claude Gronfier. Since
inadequate exposure to natural light is
the main cause of dysregulation of circadian rhythm, phototherapy remains
the standard treatment. Administering
exogenous melatonin could also be envisaged. However, as for many sleeprelated problems, the best way of
protecting yourself is to keep regular
sleeping habits and get enough exposure
©©Garo /Phanie
have been allowed to sleep normally",
notes Sylvaine Artero . Working with
her group at La Colombière Hospital in
Montpellier, the scientist was able to extract new information from the epidemiological findings of the Trois cités (3C)
study which followed elderly subjects
for 15 years. Analyzing links between
marked diurnal drowsiness and medication use, "it emerged that people who
slept better took fewer medications to
treat fungal and parasitic infections. The
actual incidence of viral and bacterial infection could not be established because
antibiotics and antiviral drugs are often
used inappropriately, but the possibility
is worth investigating", notes Sylvaine
Artero. Although evidence of weakening of the immune system seems to be
building up, the underlying physiological mechanisms remain unclear.
Be they physiological or psychological, diverse factors can interfere with
sleep. Among these, special interest is
accorded to the disruption of circadian rhythms, due to the potentially
adverse consequences that this may
entail. The most familiar is phase retardation which is common in teenagers
and young adults whose sleeping hours
get progressively delayed as their biological clock slows down. "These young
people tend to go to bed very late and
wake up spontaneously at the end of the
morning. Obliged to get out of bed in
the morning, their sleep debt builds up
causing drowsiness, learning difficulties
and emotional disturbance", emphasizes
Claude Gronfier. Inversely, sleep phase
may shift in the other direction in elderly
people, who go to bed and get up very
early. Working different shifts can also
interfere with circadian rhythm. A number of analyses have shown that workers
who alternate day and night shifts are
more susceptible to disease than others due to the deregulation of their biological clocks. In a recent report on the
health effects of night-shift work, the
Agence nationale de sécurité sanitaire
de l’alimentation, de l’environnement
et du travail (Anses, National Agency
for Food, Work & the Environment)
highlighted the adverse effects on cognitive function, mental health, diabetes,
cardiovascular disease and cancer. The
Centre international de recherche sur
le cancer (CIRC, International Cancer
15
to natural light. It is important to learn
to listen to your body and find its natural rhythms. Sleep should be respected
not as a waste of time but rather as a
way of staying healthy. n
To find out more
17th National Sleep Day 17 March 2017
www.journeedusommeil.org
Sylvaine Artero: Inserm Unit 1061/CNRS – Université
Montpellier
2Journal of Sleep Research, September 2016, 25 Issue Supplement S1;
1: 5-376, doi: 10.1111/jsr.12446.
2C. Berticat et al. Scientific Reports, 21 March 2016,
doi: 10.1038/srep23574
2Anses, June 2016, Evaluation of health problems related to nightshift work
2F. Menegaux et al. International Journal of Cancer, 15 February 2013,
doi: 10.1002/ijc.27669. E
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