Modulation of Sleep by Obesity, Diabetes, Age, and Diet

357 Pages·2014·12.894 MB·English

by  Ronald Ross Watson

Modulation of Sleep by
Obesity, Diabetes, Age,
and Diet
Edited by
Ronald Ross Watson
University of Arizona, Tucson, AZ, USA
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Top right image on cover. One night of sleep deprivation is associated with reduced glucose metabolism (blue regions) within the
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Contributors
Q.A. Altaf Centre of Endocrinology, Diabetes and Maida Lynn Chen Division of Pulmonary and Sleep
Metabolism, University of Birmingham, Birmingham, Medicine, University of Washington School of Medicine,
UK; Department of Diabetes and Endocrinology, Heart Seattle Children’s Hospital, Seattle, WA, USA
of England NHS Foundation Trust, Birmingham, UK
Alison Coates Nutritional Physiology Research Centre,
Francesco Angelico Department of Public Health and Sansom Institute for Health Research, University of
Infectious Diseases, Sapienza University, Rome, Italy South Australia, Adelaide, SA, Australia
Enrique Calvo Ayala Division of Pulmonary and Critical Flávia C. Corgosinho Programa de Pós-Graduação em
Care Medicine, Eastern Virginia Medical School, Nutrição, Universidade Federal de São Paulo, São
Norfolk, VA, USA Paulo, Brazil
Siobhan Banks Centre for Sleep Research, University of Renzhe Cui Public Health, Department of Social and
South Australia, Adelaide, SA, Australia Environmental Medicine, Graduate School of Medicine,
Osaka University, Suita-City, Osaka, Japan
Francesco Baratta Department of Internal Medicine
and Medical Specialties, Sapienza University, Rome, Ana R. Dâmaso Programa de Pós-Graduação em
Italy Nutrição, Universidade Federal de São Paulo, São
Paulo, Brazil
Kelly G. Baron Feinberg School of Medicine,
Northwestern University, Chicago, IL, USA Alessandra Danese Department of Neurological,
Neuropsychological, Morphological and Movement
Maria Rosaria Bonsignore Dipartimento Biomedico di
Sciences, University Hospital of Verona, Verona,
Medicina Interna e Specialistica (DiBiMIS), Università
Italy
di Palermo, Palermo, Italy; Istituto di Biomedicina e
Immunologia Molecolare (IBIM), Consiglio Nazionale Maria Del Ben Department of Internal Medicine
delle Ricerche (CNR), Palermo, Italy and Medical Specialties, Sapienza University, Rome,
Italy
Susan L. Calhoun Sleep Research & Treatment Center,
Penn State Milton S. Hershey Medical Center, College Jillian Dorrian Centre for Sleep Research, University of
of Medicine, Pennsylvania State University, Hershey, South Australia, Adelaide, SA, Australia
PA, USA
Alfred Dreher Department of Otorhinolaryngology, Ludwig-
Violeta Alejandra Castaño-Meneses Clínica de Trastornos Maximilians-University, Munich Germany
del Dormir, Departamento de Neurología y Psiquiatría,
Dan Eisenberg Department of Surgery, Stanford School of
INCMNSZ, México City, México
Medicine and Palo Alto VA Health Care System, Palo
Alessandra Castrogiovanni Dipartimento Biomedico di Alto, CA, USA
Medicina Interna e Specialistica (DiBiMIS), Università
Julio Fernandez-Mendoza Sleep Research & Treatment
di Palermo, Palermo, Italy
Center, Penn State Milton S. Hershey Medical Center,
Peter Celec Institute of Molecular Biomedicine, Comenius College of Medicine, Pennsylvania State University,
University, Bratislava, Slovakia; Center for Molecular Hershey, PA, USA
Medicine, Slovak Academy of Sciences, Bratislava,
Marta Garaulet Department of Physiology, University of
Slovakia; Institute of Pathophysiology, Comenius
Murcia, Murcia, Spain
University, Bratislava, Slovakia; Department of
Guillermo García-Ramos Departamento de Neurología y
Molecular Biology, Comenius University, Bratislava,
Psiquiatría, INCMNSZ, México City, México
Slovakia
xiii
xiv Contributors
Purificación Gómez-Abellán Department of Physiology, Helena Igelström Department of Public Health and Caring
University of Murcia, Murcia, Spain Sciences, Uppsala University, Uppsala, Sweden
Crystal Grant Centre for Sleep Research, University of Yuichi Inoue Department of Somnology, Tokyo Medical
South Australia, Adelaide, SA, Australia University, Shinjuku-ku, Tokyo, Japan
Guido Grassi Clinica Medica, San Gerardo Hospital, Hiroyasu Iso Public Health, Department of Social and
University of Milano Bicocca, Monza, Milan, Italy Environmental Medicine, Graduate School of Medicine,
Wendell A. Grogan Kingwood Neurology and Sleep, Osaka University, Suita-City, Osaka, Japan
Kingwood, TX, USA Ashutosh Kaul Department of Surgery, Westchester
Claudia Irene Gruttad’Auria Dipartimento Biomedico di Medical Center, Valhalla, NY, USA
Medicina Interna e Specialistica (DiBiMIS), Università Shannon R. Kenney Center for Alcohol and Addiction
di Palermo, Palermo, Italy Studies, Department of Behavioral and Social Sciences,
Zeynep Güneş School of Health, Adnan Menderes Brown University School of Public Health, Providence,
University, Aydın, Turkey RI, USA
Ilana S. Hairston School of Behavioral Sciences, William D.S. Killgore Center for Depression, Anxiety, and
Academic College of Tel Aviv-Jaffa, Tel Aviv, Israel Stress Research, McLean Hospital, Harvard Medical
School, Belmont, MA, USA
Fahed Hakim Department of Immunology, Technion,
Israel Institute of Technology, Haifa, Israel; Rambam Yoko Komada Department of Somnology, Tokyo Medical
Health Care Campus, Haifa, Israel University, Shinjuku-ku, Tokyo, Japan
Ahmad O. Hammoud M.P.H, University of Utah, Salt B. Santhosh Kumar Department of Pathology, Sree Chitra
Lake City, UT, USA Tirunal Institute for Medical Sciences and Technology,
Thiruvananthapuram, Kerala, India
Hans-Ulrich Häring Department of Internal Medicine,
Division of Endocrinology, Diabetology, Vascular Nancy Linford Department of Molecular and Integrative
Disease, Nephrology and Clinical Chemistry, University Physiology, University of Michigan, Ann Arbor, MI, USA
of Tuebingen, Baden-Württemberg, Germany German
António Macedo Faculty of Medicine, Department of
Center for Diabetes Research (DZD), Tuebingen,
Psychological Medicine, University of Coimbra,
Baden-Württemberg, Germany; Institute for Diabetes
Coimbra, Portugal
Research and Metabolic Diseases of the Helmholtz
Anthony Maffei Department of Surgery, Westchester
Center Munich at the University of Tuebingen (IDM),
Medical Center, Valhalla, NY, USA
Tuebingen, Baden-Württemberg, Germany
Paul E. Marik Division of Pulmonary and Critical Care
Shelby Harris Behavioral Sleep Medicine Program
Medicine, Eastern Virginia Medical School, Norfolk,
Sleep-Wake Disorder Center at the Montefiore Medical
VA, USA
Center, Albert Einstein College of Medicine, Bronx,
NY, USA Anna Maria Marotta Dipartimento Biomedico di
Medicina Interna e Specialistica (DiBiMIS), Università
Ashfaq Hasan Department of Pulmonary Medicine,
di Palermo, Palermo, Italy
Deccan College of Medical Sciences/Owaisi Hospital
and Research Centre, Hyderabad, India Oreste Marrone Istituto di Biomedicina e Immunologia
Molecolare (IBIM), Consiglio Nazionale delle Ricerche
Georgina Heath Centre for Sleep Research, University of
(CNR), Palermo, Italy
South Australia, Adelaide, SA, Australia
Nobuhide Matsuoka Department of Surgery, Westchester
Július Hodosy Institute of Molecular Biomedicine,
Medical Center, Valhalla, NY, USA
Comenius University, Bratislava, Slovakia; Center for
Molecular Medicine, Slovak Academy of Sciences, Emilia Mazzuca Dipartimento Biomedico di Medicina
Bratislava, Slovakia; Institute of Physiology, Comenius Interna e Specialistica (DiBiMIS), Università di
University, Bratislava, Slovakia Palermo, Palermo, Italy
Winni F. Hofman Department of Psychology, Brain Marco T. de Mello Universidade Federal de Minas Gerais,
and Cognition Group, University of Amsterdam, Belo Horizonte, Minas Gerais, Brazil
Amsterdam, The Netherlands
Babak Mokhlesi Sleep, Metabolism, and Health Center,
Heather E. Howe University of Utah, Salt Lake City, UT, Department of Medicine, University of Chicago,
USA Chicago, IL, USA
Contributors xv
Center Munich at the University of Tuebingen (IDM),
Imrich Mucska Sleep Laboratory, University Hospital,
Tuebingen, Baden-Württemberg, Germany
Bratislava, Slovakia
Gino Seravalle Cardiology Department, S. Luca Hospital,
Giacomo Mugnai Department of Cardiology, University
IRCCS Istituto Auxologico Italiano, Milan, Italy;
Hospital of Verona, Verona, Italy
Clinica Medica, San Gerardo Hospital, University of
Forrest H. Nielsen U.S. Department of Agriculture,
Milano Bicocca, Monza, Milan, Italy
Agricultural Research Service, Grand Forks Human
Hossein Sharafkhaneh Kingwood Research Institute,
Nutrition Research Center, Grand Forks, ND, USA
Kingwood, TX, USA
Heather Carmichael Olson Division of Child Psychiatry,
Maria João Soares Faculty of Medicine, Department
University of Washington School of Medicine, Seattle
of Psychological Medicine, University of Coimbra,
Children’s Hospital and Research Institute, Seattle, WA,
Coimbra, Portugal
USA
Marie-Pierre St-Onge Department of Medicine, College
Daniele Pastori Department of Internal Medicine and
of Physicians and Surgeons, Columbia University,
Medical Specialties, Sapienza University, Rome, Italy
New York, NY, USA; New York Nutrition Obesity
Amee A. Patel Department of Sleep Medicine, Baylor
Research Center, Mount Sinai St. Luke’s, New York,
College of Medicine, Houston, TX, USA
NY, USA
Amanda J. Piper Department of Respiratory and
Krishna M. Sundar Sleep-Wake Center, University of
Sleep Medicine, Royal Prince Alfred Hospital,
Utah, Salt Lake City, UT, USA
Camperdown, NSW, Australia; Sleep and Circadian
Abd A. Tahrani Centre of Endocrinology, Diabetes
Group, Woolcock Institute of Medical Research,
and Metabolism, University of Birmingham,
Glebe, NSW, Australia
Birmingham, UK; Department of Diabetes and
Licia Polimeni Department of Public Health and Infectious
Endocrinology, Heart of England NHS Foundation
Diseases, Sapienza University, Rome, Italy; Department
Trust, Birmingham, UK
of Internal Medicine and Medical Specialties, Sapienza
Lucia M. Talamini Department of Psychology, Brain
University, Rome, Italy
and Cognition Group, University of Amsterdam,
Kathryn J. Reid Feinberg School of Medicine,
Amsterdam, The Netherlands
Northwestern University, Chicago, IL, USA
Akira Tamura Department of Cardiology and Clinical
Montserrat Resendiz-Garcia Clínica de Trastornos del
Examination, Faculty of Medicine, Oita University,
Dormir, Departamento de Neurología y Psiquiatría,
Yufu, Japan
INCMNSZ, México City, México
Michael Thorpy Sleep Wake Disorder Center at the
Asya Rolls Department of Immunology, Technion, Israel
Montefiore Medical Center, Professor of Neurology,
Institute of Technology, Haifa, Israel
Albert Einstein College of Medicine, Bronx, NY, USA
Christina L. Ruby Department of Biology, Indiana
Nazia Uzma Department of Physiology, Deccan College
University of Pennsylvania, Indiana, PA, USA
of Medical Sciences, Hyderabad, India
Victoria Santiago-Ayala Clínica de Trastornos del Dormir,
Matilde Valencia-Flores Clínica de Trastornos del Dormir,
Departamento de Neurología y Psiquiatría, INCMNSZ,
Departamento de Neurología y Psiquiatría, INCMNSZ,
México City, México
México City, México; Facultad de Psicología, UNAM,
Tina Sartorius Department of Internal Medicine, Division México City, México
of Endocrinology, Diabetology, Vascular Disease,
Arthur S. Walters Department of Neurology, Vanderbilt
Nephrology and Clinical Chemistry, University of
University, Nashville, TN, USA
Tuebingen, Baden-Württemberg, Germany; German
Leonard B. Weinstock Department of Medicine,
Center for Diabetes Research (DZD), Tuebingen,
Washington University School of Medicine, LLC, St.
Baden-Württemberg, Germany; Institute for Diabetes
Louis, MO, USA
Research and Metabolic Diseases of the Helmholtz
Acknowledgments
The work of Dr Watson’s editorial assistant, Bethany L. Stevens, in communicating and working with authors on the
manuscripts was critical to the successful completion of this book. It is very much appreciated. The encouragement,
advice, and support of Kristi Anderson and Mica Haley in Elsevier’s Neurological Books department was very help-
ful. Support for Ms Stevens’ and Dr Watson’s work was graciously provided by the Natural Health Research Institute
(www.naturalhealthresearch.org) and Southwest Scientific Editing & Consulting, LLC. Finally the work of the librarian at
the Arizona Health Science Library, Mari Stoddard, was vital and very helpful in identifying key researchers who partici-
pated in the book.
xvii
Chapter 1
Diet, Age, and Sleep in Invertebrate
Model Organisms
Nancy Linford
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
Chapter Outline
Introduction 3 Effects of Disease and Age on Sleep 7
How Do We Know that the Animal Is Sleeping? 3 Effects of Sleep on Feeding and Disease 8
Different Ways to Evaluate Sleep 4 Summary 8
Correlations between Ecological Niche and Sleep Behavior 4 References 8
Effects of Diet on Sleep 5
INTRODUCTION (Allada & Siegel, 2008; Cirelli, 2009; Crocker & Sehgal,
2010). Given the depth and quality of these reviews, I will
Diet, or the consumption of calories from the external envi-
attempt to instead focus specifically on the interconnected
ronment, is an obligatory task of all metazoans. Yet the
relationship between diet, sleep, and disease and highlight
effects of the nutritional environment are not simply a binary
major areas where more work is desperately needed.
fed/not-fed switch. The type and density of a nutrient source
can have profound secondary effects. In a medical sense, the
dietary components can be considered good or bad, either HOW DO WE KNOW THAT THE ANIMAL
preventing or enhancing the onset of disease due to both
IS SLEEPING?
caloric load and the presence of auxiliary chemicals that can
be beneficial or toxic to cells and organ systems. However, Before we launch into a discussion of how diet affects sleep
from a broader perspective, the dietary composition can also in animals vastly different from ourselves, it is important
provide essential information about the state of other attri- to consider the characteristics of sleep. How do we know if
butes of the environment. These factors may have shaped the an animal is sleeping? This remains a somewhat controver-
life history characteristics and behavioral responses of all sial issue. In 1913, Pieron proposed behavioral criteria that
organisms. For instance, the ripeness (amount of sugar) in hold up today, including (1) a typical body posture and site,
fruits can provide seasonality information. The availability (2) a behavioral state of quiescence, (3) an elevated arousal
of food may also, directly or indirectly, signal the potential threshold or reduced responsiveness to external stimuli,
presence of predators, competitors, or mates. and (4) rapid state reversibility (to distinguish sleep from
In this chapter, I will attempt to summarize our current, coma, injury, or death). Later researchers added the criteria
albeit limited, understanding of the relationship between of a homeostatic response to deprivation and responsive-
dietary factors, internal disease state, and sleep behavior in ness of the sleep periods to the circadian rhythm (Hendricks
nonhuman animals, with a particular emphasis on the inver- et al., 2000). In humans, electrophysiological correlates of
tebrate model systems where we can leverage the power of sleep have become invaluable both to positively distinguish
genetics to move forward quickly. I encourage the reader sleep from quiet wakefulness and to assess the organiza-
to investigate several excellent recent reviews on the topic tion of sleep stages throughout a period of sleep. How-
of sleep in less complicated organisms, particularly the ever, one tricky aspect of this analysis is that occasionally
genetics of sleep in Caenorhabditis elegans and Drosophila most, but not all, signs of sleep will be present, leading to
Modulation of Sleep by Obesity, Diabetes, Age, and Diet. http://dx.doi.org/10.1016/B978-0-12-420168-2.00001-6
Copyright © 2015 Elsevier Inc. All rights reserved. 3
4 PART | I Mechanisms of Sleep Deprivation and General Dietary Therapies
an ambiguous situation that becomes even more unclear Yap, Kirszenblat, Kottler, & van Swinderen, 2013; van Swin-
as we assess the impact of environmental variables. As we deren, Nitz, & Greenspan, 2004), this chapter will focus on
shall see, rules are meant to be broken. For instance, the the analysis of behavioral patterns as indicators of the sleep–
bullfrog Rana catesbeiana is notable for its daily pattern of wake relationship.
rest with no change in arousal threshold (meeting criteria One very useful broad generalization to consider when
1, 2, and 4) (Hobson, 1967). Marine mammals, particularly evaluating behavioral patterns is the reciprocal tradeoff
dolphins, show electrophysiological correlates of sleep but between exploration and exploitation that characterizes
these are only unihemispheric (one side of the brain) and behavior patterns and search strategies across a wide range
often associated with stereotyped circular motions of the of organisms. These alternating states of movement (explo-
body (meeting criteria 1 and 4) (Lyamin, Manger, Ridgway, ration to seek resources) and relative inactivity (exploita-
Mukhametov, & Siegel, 2008). Similarly, three-toed sloths, tion of the resources in a given area) are the foundation of
some cats, and many birds show electrophysiological cor- reinforcement learning theory. The exploitation phase can
relates of sleep during active waking, and sleep-deprived comprise active feeding, mating, or sleeping. In all cases,
humans will also show evidence of “sleep” while behavior- there is a behavioral switch that turns off the exploration
ally active (Campbell & Tobler, 1984). It seems clear that drive in order to promote dwelling, with sleeping being a
a completely rigid set of criteria cannot be applied to all potential extreme case of the dwelling phase where arousal
animals and special consideration must be used when fac- is at a minimum. This relationship between exploration
toring in the relationship between sleep behavior and diet. and exploitation is best characterized biochemically in
Are all of these animals “truly” sleeping? Likely not. From terms of the “rover” and “sitter” phenotype in Drosophila
the perspective of the reductionist, it may not matter or even larvae, where polymorphisms in a single gene, foraging, a
be beneficial. The reductionist will study each piece of a cyclic guanosine monophosphate (cGMP)-dependent pro-
complex behavior in the organism that is most amenable tein kinase, can tip the balance between the propensity for
to study. This approach has been remarkably successful for exploitation and exploration (Osborne et al., 1997). Given
seemingly intractable problems such as memory, neuro- that activation of the cGMP signaling pathway through
nal excitability, and cell biology and is being increasingly nitric oxide is a potent regulator of sleep behavior and
applied to complex behaviors and social interactions. cardiovascular health in mammals as well, it is likely that
these basic concepts of the exploration/exploitation axis are
retained through evolution and elaborated on to form the
DIFFERENT WAYS TO EVALUATE SLEEP
fundamentals of human sleep regulation.
When considering an analysis of the environmental effects on
sleep behavior, it is useful to consider not only the total daily
CORRELATIONS BETWEEN ECOLOGICAL
sleep duration but also other characteristics of the sleep pat-
NICHE AND SLEEP BEHAVIOR
terns, as these may impact the overall “quality” of the sleep
experience. Some, but not all, of the characteristics may be Before moving into the world of the model organisms, let
affected by the dietary environment and disease state. These us first consider the lessons of comparative biology. It is
additional characteristics include the organization of the sleep not surprising that the baseline sleep characteristics of an
behavior relative to the circadian day, the transition probabil- organism are shaped by its ecological niche. For instance,
ity either into or out of sleep, the pattern of sleep states, and the challenges of an aquatic, terrestrial, or arborial domain
the number of sleep periods in the day (pure monophasic will affect the tradeoffs that shape the stereotypical sleep
nighttime sleep appears to be a feature unique to simians). patterns. Of particular relevance for this review, the correla-
Furthermore, there are environmentally induced periods of tion between typical diet and sleep duration is interesting.
sleep such as the rebound response to prior sleep deprivation In general, there is a negative correlation between animal
and postprandial slowdowns that can share important char- size and total sleep duration in mammals. However, if we
acteristics with sleep. When considering the potential harm look more closely, the effect of body size on sleep behav-
caused by disrupted sleep, there is both a concern regarding ior has an interesting relationship with dietary consump-
the overall long-term health status and the ability to safely tion. For carnivores, there is no relationship between sleep
complete waking tasks. For instance, a change in the prob- duration and body size and sleep times are consistently
ability of falling asleep (as is seen in narcolepsy) may not greater than 8 h per day. However, there is an extreme nega-
alter total daily sleep but would greatly impair safety and tive correlation between body size and average daily sleep
lead to loss of independence in a human. The organization of time in herbivores with the largest mammals coming in at
sleep states, such as slow wave and paradoxical sleep, within under 4 h (Siegel, 2005). What is the reason for this diet-
a given sleep period can also massively impact the quality of dependent difference in sleep behavior? Is stress a factor?
sleep. However, because evidence for the existence of sleep While extremely interesting, these questions are unfortu-
states in invertebrate model systems is scant (van Alphen, nately stubborn to definitively address in wild populations.
Diet, Age, and Sleep in Invertebrate Model Organisms Chapter | 1 5
Instead, we will turn to the well-characterized genetic is lethargus, a period of behavioral quiescence and feeding
model organisms, where mechanistic hypotheses can be cessation that marks the transitions between the larval stages
tested through a combination of genetic and environmental (Raizen et al., 2008). The second is satiety-induced quies-
manipulations. Among the invertebrates, the leaders in pro- cence in the adult worm (You, Kim, Raizen, & Avery, 2008).
viding mechanistic insight are C. elegans and Drosophila In order to study this second state, worms are fasted and refed
melanogaster due largely to the wealth of genetic tools and and a massively diminished movement profile is observed,
automated equipment for assessment. As we will see, C. coupled with the cessation of pharyngeal pumping behav-
elegans sleep is more recently characterized and therefore ior. This satiety-induced sleep state depends both on a prior
has been studied less deeply than that of Drosophila, which period of fasting and on the quality of the food delivered after
meets all of the criteria for the existence of true sleep. fasting, with a nutrient-dense food being required to induce
The fields of behavioral genetics and neurobiology have the sleep-like state (Gallagher, Kim, Oldenbroek, Kerr, &
recently been obsessed with mapping out the neural circuits You, 2013). Although the relationship between this satiety-
responsible for behavioral states and making broad mecha- sleep and true sleep is tenuous (there is no way to separate
nistic interpretations about the way that organisms can pro- it from drowsiness), it offers a valuable opportunity to use
cess their environment. One reason for this enthusiasm with this powerful genetic organism in order to understand the
circuits is that evidence across widely divergent behavioral regulation of behavioral states by conserved molecular path-
processes seems to indicate that the neuronal control of ways. Furthermore, because the adult C. elegans has no other
behavior and metabolism is largely a property derived from sleep-like state, postprandial sleep can be studied in perhaps
the action specific circuits rather than a property derived its purest form. The initial forays into genetic dissection have
from the neurochemical state of the brain as a whole. Dif- returned a rough pathway for regulation. A recent report
ferent molecules and neurotransmitters have widely differ- has implicated the ASI neurons in feeding-induced sleep
ent effects depending on the neurons involved. A classic (Gallagher et al., 2013) (Figure 1). The ASI neurons are a pair
example is the role of dopamine in Drosophila appetitive of bilaterally symmetric multifunctional sensory neurons that
and aversive behavior depending on the site of activation send ciliated dendrites into the amphid organs, a pair of small
(Burke et al., 2012; Liu, Placais, et al., 2012). Thus, both external openings near the worm’s mouth, and then extend
the “what” and the “where” are important for deeply under- into the ring gland, a neuropil that serves as the worm’s brain
standing the mechanisms underlying the impact of environ- and primary secretory center (WormAtlas, 2002–2012).
mental events on important physiological processes such as These neurons are activated by the transition from fasting
sleep. to feeding, as measured by calcium imaging. Overall, the
authors used standard genetic disruption in combination with
genetic cell ablation using reconstituted caspases (Chelur &
EFFECTS OF DIET ON SLEEP
Chalfie, 2007) to assemble a putative mechanism. They
Two types of quiescent periods have been identified in C. found an interesting switching mechanism where the RIM
elegans and purported to represent aspects of sleep. The first and RIC neurons constitutively release an unknown hunger
ASI neurons off FIGURE 1 Regulation of Caenorhabditis elegans
RIM & RIC neurons on postprandial sleep. A close-up view of the head and
Starved pharynx area shows the RIM and RIC neurons on under
?
starvation conditions (top) and the release of unknown
Locomotion locomotion-promoting signals into the circulation. When
? food becomes available, the ASI neurons activate (bot-
TGFβR/DAF-1 tom) and release transforming growth factor (TGF)β/
DAF-7, which binds the TGFβR/DAF-1 and promotes
sleep-like quiescence.
TGFβ/DAF-7
+ Caenorhabditis elegans
TGFβR/DAF-1
Fed
Sleep
ASI neurons on
RIM & RIC neurons off
6 PART | I Mechanisms of Sleep Deprivation and General Dietary Therapies
signal in the absence of food. When food is perceived, the well known that food deprivation increases activity and pro-
ASI neuron activates and releases transforming growth fac- motes foraging in a range of animals, including Drosoph-
tor (TGF)β/DAF-7. This release suppresses the activity of the ila (Lee & Park, 2004). Keene et al. (2010) demonstrated
RIM and RIC neurons. cGMP generation and insulin release that lack of food specifically impairs sleep behavior. They
are also required, although the location of these signals in went on to identify a set of cryptochrome-positive neurons
the neuronal circuit remains unclear (You et al., 2008). This that had been previously implicated in circadian regulation
simple circuit, when considered as a “wiring diagram,” can of locomotion as being crucial for the regulation of sleep
provide basic insights into how an organism may receive and under nutrient stress conditions. This initial finding has
process environmental information. Furthermore, because opened the door for more detailed work on the mechanisms
the biochemical main players have vertebrate homologs that underlying tradeoffs between the need to seek food and the
are regulators of sleep behavior, it is likely that this basic need to sleep. More recently, Erion, DiAngelo, Crocker,
information will hold true across phyla. In particular, the and Sehgal (2012) implicated octopamine (the invertebrate
relationship between TGFβ and sleep behavior in humans is functional analog of norepinephrine) in a circuit regulating
not well established and awaits follow-up in a mammalian sleep deprivation in an interesting pathway that mechanis-
system. These initial forays have begun to map the regulation tically separates fat storage (insulin dependent) and sleep
of sleep behavior and we can look forward to genetic screens behavior (insulin independent).
that use simple behavioral assays to identify novel regulators Our laboratory has also addressed the relationship
of post-prandial sleep behavior that may also have vertebrate between nutrient type and density and sleep behavior and
functional homologs. found that modulating either sugar or yeast did not alter
The other major invertebrate model system for studying total sleep or its distribution between night and day but that
the effects of the environment on sleep is D. melanogaster. sugar had a strong ability to regulate the length of sleep
Here, we are particularly lucky because the genetics and bouts through a mechanism involving gustatory percep-
neuroanatomy of circadian locomotor behavior are excep- tion and a second sensory-independent mechanism that
tionally well studied and the genetics of sleep are moving was activated depending on the nutrient density of the food
very rapidly. This organism is increasingly used to model (Linford, Chan, & Pletcher, 2012). This result indicates that
human disease, and approximately 75% of known disease different nutrients have qualitatively different effects on
genes have homologs in Drosophila (Reiter, Potocki, Chien, sleep behavior and that animals can respond not only to the
Gribskov, & Bier, 2001). The relationship between food availability of food but also to its type and quality in order
intake and sleep behavior is less clear, but various pieces to regulate sleep behavior.
of the puzzle are starting to come together (Figure 2). It is To date, there is no clear model in Drosophila for post-
prandial sleep, similar to that in mammals and C. elegans.
There have been additional reports of a very high pro-
(cid:36) (cid:37) tein diet either increasing or suppressing total daily sleep
(cid:38) amount in Drosophila (Catterson et al., 2010; Katewa et al.,
(cid:39) 2012) as well as a related Queensland fruit fly (Fanson,
(cid:40) Petterson, & Taylor, 2013). We have since investigated the
situation in more detail and found that the high protein–
induced sleep behavior is most pronounced immediately
(cid:54)(cid:79)(cid:72)(cid:72)(cid:83) following feeding. Interestingly, these results may indicate
that Drosophila, too, is a candidate for the study of post-
(cid:40)(cid:91)(cid:87)(cid:72)(cid:85)(cid:81)(cid:68)(cid:79)
prandial sleep.
(cid:42)(cid:88)(cid:86)(cid:87)(cid:68)(cid:87)(cid:82)(cid:85)(cid:92)(cid:3)(cid:83)(cid:72)(cid:85)(cid:70)(cid:72)(cid:83)(cid:87)(cid:76)(cid:82)(cid:81)
(cid:48)(cid:72)(cid:70)(cid:75)(cid:68)(cid:81)(cid:82)(cid:86)(cid:72)(cid:81)(cid:86)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81) While the relationship between dietary intake and sleep
(cid:44)(cid:81)(cid:87)(cid:72)(cid:85)(cid:81)(cid:68)(cid:79) is only beginning to emerge in Drosophila, the neurogenet-
(cid:47)(cid:72)(cid:83)(cid:87)(cid:76)(cid:81)(cid:18)(cid:56)(cid:51)(cid:39)(cid:21) ics of feeding and satiety regulation are being well-studied
(cid:41)(cid:85)(cid:88)(cid:70)(cid:87)(cid:82)(cid:86)(cid:72)
in other contexts and these may provide important insights
into sleep behavior. Krashes et al. (2009) found a mecha-
nism for the regulation of satiety-induced loss of feeding
FIGURE 2 Regulation of nutrient status in Drosophila. Inputs from
motivation that involves Npf (the insect version of neuro-
the external environment (gustatory perception, mechanoperception)
and the internal environment (LEPTIN/UPD2, fructose) send infor- peptide Y) neuron activation in the absence of food, block-
mation to the brain. This information is processed in distinct sites ing an inhibitory signal from a population of dopaminergic
including (A) the dorsal cryptochrome-positive cells that respond to neurons that feed into the mushroom body, a site of neuro-
starvation, (B) the medial neurosecretory cells that secrete insulin-like
nal plasticity and memory storage. This relief from inhibi-
peptides, (C) the fan-shaped body that regulates some aspects of sleep,
tion mechanism will undoubtedly inform a growing map of
(D) the ellipsoid body that contains hunger-regulatory cells, and (E) the
subesophageal ganglion that processes gustatory information. the relationship between external events and internal state.