Productive Sleep doesn’t have to be just a dream.

Introducing Life Priority’s Productive Sleep™

Good sleep doesn’t have to be just a dream. Get more power from your nap! Get more out of the sleep you get.

By Durk Pearson & Sandy Shaw

Hundreds of substances, both natural and synthetic, have been tried over the past few thousand years as sleep-inducing agents. Many were successful in inducing unconsciousness. Why, then, did they generally fail to provide the user with a feeling of rested refreshment the next morning? The answer is complex, but the bottom line is that no one substance can perform the very complex task of helping you to have a more refreshing nap or night’s sleep.

SLEEP is far more than a daily period during which you lapse into a lengthy state of unconsciousness. It is a highly programmed mental state that engages all parts of your brain in a complex pattern of activity. “… sleep is no longer considered a passive resting state, but rather an active brain state essential for neuronal plasticity.”¹ If all has gone well, you awake with a sense of refreshment and well-being, having been prepared for a new day by a night of productive sleep.
New research has reported beneficial effects on cognition (particularly memory) of daytime naps, as well.

Our new sleep formulation Productive Sleep is designed to equip your brain with supplies of sleep-enhancing natural substances to help make it easy to just let go and slip into a daytime nap or nighttime sleep without a struggle, even at the end of or during a day that may be full of hard work and stressful events. Then, after you fall asleep, Productive Sleep helps your brain navigate nature’s restorative sleep pathways. We designed Productive Sleep for our own personal use because there are a lot of things to worry about these days and we really need good sleep. Productive Sleep works for us. Several of our best friends have reported enthusiastically on the effects of Productive Sleep.

Reference
1. Lepousez and Liedo. Life and death decision in adult neurogenesis: in praise of napping. Neuron. 71:768-71 (2011).

What Does Good Sleep Do For You Besides Produce a State of Restedness and Energy When You Wake Up?
Underneath the surface of feeling rested and ready to proceed with a new day’s activities is where all the action is, the complex biochemical processes resulting from a night of the right amount of physiological sleep. Not surprisingly, there is much yet to be learned about how sleep works, but some things are becoming much clearer. A major result of sleep is now known to be a process of re-experiencing memories and restoring them into long-term storage.^1–4 Another important process involves the creation of new adult-born neurons (neurogenesis)⁵ that allows two (known) critical brain areas to continue to produce neurons throughout life. These new neurons are particularly important for vigorous youthful function as compared to old early-born neurons.

“… sleep is no longer considered a passive resting state, but rather an active brain state essential for neuronal plasticity.”

 Sleep Preserves Memories
A new study⁵ along with a commentary on that paper⁶ reports that the sleepiness that often follows a meal and results in a daytime nap has been found to contribute to synaptic plasticity by …
promoting dampening of potentiated synapses during awake state to minimize their energy consumption, reduce their physical volume, and prevent their strength from saturating. Thus, synaptic depression or downscaling during sleep may recalibrate synaptic weights down to a more responsive range. In parallel to this homeostatic process, sleep has been shown to contribute to memory consolidation. Notably, repeated reactivation of activity patterns evoked during learning [when awake] has been observed during slow-wave sleep both in rats and humans.⁶
This reactivation is called “replay” and may be essential to the preservation of memories in long-term storage.

“The results suggest that sleep—even as brief as a nap—facilitates the reorganization of discrete memory traces into flexible relational memory networks.”

Improved Reactivation of Information Acquired During the Wake State Via The Power Nap
A new study^6A reports on how learning a skill can be improved by an afternoon nap. People learned to produce two melodies in time with moving visual symbols by pressing four keys in time with repeating 12-item sequences of moving circles. Then, when an EEG indicated that a subject was in slow wave sleep during an afternoon nap, one of the melodies was covertly presented 20 times over a 4-minute interval. The performance of the melody presented during the nap (called the cued melody) was found to be played more accurately when the subjects awoke. In subjects who also practiced the two melodies but slept during the afternoon nap without a cued melody, the average playing after awakening improved as well, in correlation with the amount of time spent in slow wave sleep, but not to the degree of improvement shown by those exposed to the cued melody during slow-wave sleep.

“Our [Lau et al, 2011] results make clear that sleep is important for the abstraction of generality.”

The authors explain that prior studies have shown a strengthening of spatial associative memory from learning-related cues presented during slow-wave sleep. Thus, the new study extended the earlier findings by showing that “auditory cues can selectively change the ability to perform a distinct type of sensorimotor skill memory.”^6A

The researchers did not test during other stages of sleep, noting that slow wave sleep “has been recognized as being critical for systems memory consolidation.”^6A
Another paper^6B reported on a daytime nap study in which subjects had to learn the English meanings of Chinese characters with overlapping semantic components called radicals. When they were later tested on new characters that they had never seen before but which shared the same radicals, they had to show that they understood the general concepts represented by the radicals; the participants that took naps, whether they took place immediately after learning or following a delay, performed better. “The results suggest that sleep—even as brief as a nap—facilitates the reorganization of discrete memory traces into flexible relational memory networks.” “Our results make clear that sleep is important for the abstraction of generality.”^6B

Sleep and Neurogenesis Part of the neurogenesis process is the production of new neurons, of course, but also the paring of the population of new neurons by controlled death (apoptosis) of some of these newborn cells. This complex process is just beginning to be understood. The new paper⁵ found that while the apoptosis of newly born neurons is constant over time in mice allowed unlimited access to food, the number of apoptotic neurons is increased strongly after eating when food is restricted to a limited time period (4 hours). Thus, the new neurons are being constantly turned over. However, a postprandial nap (sleep following a meal) also resulted in a potentiation in the rate of apoptosis in the new neurons. This was experimentally shown by preventing the animals from sleeping after a meal, which resulted in the prevention of apoptosis of the newly formed neurons. The regulation of the process of apoptosis is critically dependent upon LEARNING taking place in the newborn neurons, with learning supporting the survival of these neurons. The critical period of learning is 14 to 35 days after cell birth for promotion of survival, while immature (7 to 13 day cells) and cells older than the critical period are not affected.⁵

“It is only when sensory experience is associated with learning or with postprandial sleep, two processes that involve top-down inputs to the OB [olfactory bulb], that it can affect apoptosis.”⁶
Interestingly, the process in the olfactory bulb of neuronal birth, apoptosis of some newborn neurons, and the survival of the rest is all a part of the process essential for optimal olfactory exploration and for correct odor discrimination. As the authors of the commentary paper⁶ explain, during the awake state olfactory experience “tags” a subpopulation of newborn neurons from which a select group will be actively supported to survive during subsequent sleep where they will receive a “reorganizing” signal.

In summation, “sleep is no longer considered a passive resting state, but rather an active brain state essential for neuronal plasticity.”⁶

References
1. Maquet et al. Be caught napping: you’re doing more than resting your eyes. Nat Neurosci. 5(7):618-9 (2002).
2. Mednick et al. The restorative effect of naps on perceptual deterioration. Nat Neurosci. 5(7):677-81 (2002).
3. Lau et al. Relational memory: a daytime nap facilitates the abstraction of general concepts. PLoS ONE. 6(11):e27139 (2011).
4. Payne. Sleep on it!: stabilizing and transforming memories during sleep. Nat Neurosci. 14(3):272-4 (2011).
5. Yokoyama et al. Elimination of adult-born neurons in the olfactory bulb is promoted during the postprandial period. Neuron. 71:883-97 (2011).
6. Lepousez and Liedo. Life and death decision in adult neurogenesis: in praise of napping. Neuron. 71:768-71 (2011).
6A. Antony et al. Cued memory reactivation during sleep influences skill learning. Nat Neurosci. 15(8):1114-6 (2012).
6B. Lau et al. Relational memory: a daytime nap facilitates the abstraction of general concepts. PLos ONE. 6(11):e27139 (Nov. 2011).
Reduced Capacity for Sleep With Age
Another paper⁷ reports differences in sleep capacity with age in a study of 18 older subjects (12 males, 6 females, 60–78 years, mean age 67.8 ± 4.3 years) and 35 younger subjects (17 males, 18 females, 18–32 years, mean age 21.9 ± 3.3 years). All subjects were healthy and had no sleep complaints or sleep disorders.

“Sleep is no longer considered a
passive resting state, but rather
an active brain state essential for
neuronal plasticity.”
The authors report: “Total daily sleep duration, which was initially longer than habitual sleep duration, declined during the [3–7 days of the] experiment to asymptotic values that were 1.5 hr shorter in older (7.4 ± 0.4 SEM, hour) than in younger subjects (8.9 ± 0.4). Rapid-eye-movement sleep contributed about equally to this reduction [in the older subjects].” Thus, the authors concluded that under conditions of sleeping freely (with no conditions of constraint), both daytime sleep propensity and the maximal capacity for sleep are reduced in older subjects, with the obvious implication that older subjects may be more likely to experience insomnia or have other sleep problems. The researchers report studies documenting changes in the quality of sleep across the lifespan that includes decreases in nighttime sleep, polysomnographically assessed reductions in slow wave (NREM sleep stages 3 and 4), and increased daytime sleep. However, as the authors note, the understanding of what these changes mean is limited. For example, if older people need less sleep than younger ones, then less sleep might be appropriate. It is certainly the case that infants need a great deal more sleep than adults do.
Reference

7. Klerman and Dijk. Age-related reduction in the maximal capacity for sleep—implications for insomnia. Curr Biol. 18:1118-23 (2008).

The Sleep-Wake Cycle—Some Facts
The complexity of the sleep wake cycle—what is currently known of it—would be impractical for review here. Instead, we provide some key features of current understanding.
One excellent review⁸ of the sleep-wake cycle provides the following facts:
(1) There are two basic forms of sleep: slow-wave sleep (SWS) and rapid eye movement (REM) sleep. REM sleep is sometimes called paradoxical sleep because of the atonia (paralysis) of postural muscles along with twitching and episodic bursts of sacchades of quick conjugate eye movements that accompanies it.
Our comment: Although your muscles are normally immobile during REM, you can of course have dreams full of physical action. In some sleep disorders, muscular activity breaks through and can become part of the action during REM, e.g., you can dream you are kicking somebody and wake up to find you have kicked something or somebody.
(2) The review identifies several populations of wake-promoting neurons in the hypothalamus, including those in the basal forebrain, lateral hypothalamus, and tuberomammillary nuclei. Some of these neurons contain acetylcholine, which participates in arousal input to the cerebral cortex during waking. The lateral hypothalamus is identified as a possible “wake switch” that allows the hypothalamus to control the transition from sleep to wakefulness by firing at the start of the transition. Neurotransmitters involved in the waking process include adrenergic, histaminergic, dopaminergic, and cholinergic.
(3) The orexin neuropeptide (also called hypocretin) is an important waking factor. The review mentions that there are only a few thousand neurons in the lateral hypothalamus that express this neuropeptide. The brain disorder narcolepsy, where humans and some animals, such as dogs and even mice, can fall asleep suddenly in the middle of performing an action, is due to a deficiency in orexin. A human autopsy study on narcoleptic individuals was said to show a reduction in the number of orexin-containing cells by 85–95% as compared with normal individuals.⁸
(4) Natural substances that are involved in the induction and maintenance of sleep include GABA, glycine, acetylcholine (responsible for the muscle atonia during REM, for example), adenosine (caffeine and other methylxanthines are adenosine antagonists, which is one reason they can keep you awake), and certain prostaglandins. Curiously, prostaglandin D2 has been identified as a potent inducer of sleep but is also the prostaglandin released by niacin that causes flushing.
Our comment: The time profile of the release of prostaglandin D2 when inducing sleep may be different from the very short-term effect it has during niacin flushing. We don’t know. Though we both find the niacin flush to induce a transient feeling of well-being, it doesn’t put us to sleep. We do, however, take a dose of niacin at bedtime. Still, it is interesting to note that the drop in core body temperature that occurs at the onset of sleep is associated with increased cutaneous (skin) blood flow. The niacin flush also increases cutaneous blood flow.
Reference

8. Murillo-Rodriguez et al. Mechanisms of sleep-wake cycle modulation. CNS Neurol Disord Drug Targets. 8:245-53 (2009).

Sleep Deprivation Impairs cAMP Signaling in the Hippocampus
Many studies have examined sleep-deprived animals and people to help identify sleep mechanisms and to develop treatments for cognitive problems associated with sleep deficiency.
One recent paper⁹ identified impaired cAMP (cyclic AMP) signalling in the hippocampus of sleep deprived C57BL/6J male mice (2–5 months of age). cAMP is an important participant in learning and memory including the process called long-term potentiation (LTP) in the hippocampus. The reduced cAMP in the hippocampi of the mice was associated with increased levels of phosphodiesterase-4, an enzyme that degrades cAMP. Thus, the treatment of the mice with a phosphodiesterase-4 inhibitor drug rolipram “rescued” the sleep-deprived deficit in cAMP signalling, synaptic plasticity, and hippocampus-dependent memory. It is interesting to note that phosphodiesterase inhibitors are used in the treatment of many diseases. For example, Viagra is an inhibitor of phosphodiesterase-5, which degrades cGMP that is required for male erection.
The researchers explain that “circadian oscillation of cAMP in the hippocampus has recently been linked to the persistence of memory, so such drugs [phosphodiesterase-4 inhibitors] may also be useful in treating memory deficits associated with alterations in circadian rhythms.” They didn’t mention jet lag, but that is certainly an obvious situation experienced by most, if not all, readers of this publication, in which disruption of circadian rhythms can result in memory deficits.
Reference

9. Vecsey et al. Sleep deprivation impairs cAMP signalling in the hippocampus. Nature. 461:1122-1125 (2009)
   Melatonin May Prevent the Memory Deficits Associated with Total Sleep Deprivation in Rats
   A key sleep-promoting substance is melatonin, produced in and released from the pineal gland. It is known to have effects on circadian rhythms and immune function and to have antioxidative and neuroprotective properties.⁹
   After total sleep deprivation for five days (using an apparatus that forces the animals to stay awake and in motion in order to avoid being dumped into water), the expression of SIRT1 (sirtuin 1) and COX (cyclooxygenase, which occurs in two forms: COX1 and COX2) were drastically decreased in a recent study.⁹ SIRT1 is an important regulator of neuronal plasticity and is highly neuroprotective, among other things, and a deficit in its expression can lead to cognitive impairment and oxidative stress.⁹ SIRT1 is also the famous longevity protein found in studies in some animal models of aging to increase lifespan. The expression of SIRT1 is increased by the equally famous resveratrol, found in red wine, tea, and cocoa.
   During the five days of total sleep deprivation, the experimental rats received either no melatonin or various doses of melatonin (5, 25, 50, or 100 mg/kg of body weight) via intraperitoneal injections once daily. All of the tested doses of melatonin caused a significant increase in the activity of SIRT1 and COX as compared to controls receiving no melatonin. Effects were more significant at the higher doses of melatonin. The animals subject to total sleep deprivation that received no melatonin showed impaired performance in the Morris water maze test. Interestingly, while the animals totally sleep deprived were impaired in finding the hidden platform in the Morris water maze, they took nearly identical lengths of time (compared to the sleep deprived but melatonin treated animals) to reach a visible platform. Thus, the authors conclude, the total sleep deprivation caused a spatial learning deficit rather than causing some sort of sensorimotor disability.
   We have not included melatonin or 5-hydroxytryptophan in this formulation because we wanted the formula to be useful for enhancing short daytime naps. Melatonin, tryptophan, or 5-hydroxytryptophan can be used to very good effect when taken at bedtime.

Reference

10. Hung-Ming Chang et al. Melatonin preserves longevity protein (sirtuin 1) expression in the hippocampus of total sleep-deprived rats. J Pineal Res. 47:211-20 (2009).
    Regulation of Proinflammatory Cytokines by the Circadian Clock Protein Cryptochrome
    A growing number of papers exploring the mechanisms that help explain detrimental effects of sleep disruption or deprivation are being published. Another new one,¹¹ noting the increased susceptibility of people suffering from sleep deprivation to inflammation-associated diseases such as diabetes, obesity, and cancer, led researchers to examine the effects of double knock out (knocking out both CRY1 and CRY2, the genes for CRY, the core clock component protein cryptochrome, in mice and in knockout cells. The bottom line was that “the absence of the core clock component protein cryptochrome (CRY) leads to constitutive elevation of proinflammatory cytokines in a cell-autonomous manner. We observed a constitutive NF-kappaB and protein kinase A (PKA) signalling activation in CRY1-/-; CRY2-/- cells.”¹¹
    As the researchers explain, “secretion of cytokines, TNF-alpha and IL-6 has been reported to display circadian oscillation in macrophages, where ~8% of transcriptome [molecules acting as transcription regulators] is under circadian regulation. Clinical evidence and sleep-loss studies have identified physiological connections between the circadian clock and immune system.”¹¹
    Just another reason to get good restorative sleep!

Reference

11. Narasimamurthy et al. Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. Proc Natl Acad Sci USA. 109(31):12662-7 (2012)

Toward Better Sleep Quality
We know of no sleep-promoting remedy, including our own, that has actually been tested experimentally for its effects on all these cognitive and emotional processes that have been reported to take place during sleep. Fortunately, you can detect how well you slept by how you feel and perform when you wake up and later during the day. That’s a pretty reliable test for good quality sleep. It also has the great advantage of not requiring you to wait for the FDA to approve anything!

 “If you sleep till noon, you have no right to complain that the days are short.”
— Thomas Fuller, Gnomologia
© Copyright Durk Pearson & Sandy Shaw, 2013

To Your Health!

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities. rev. 9.3.2013

Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.