A Meal and a Nap are All I Need

By Samantha Wong

Consider the thalamus. A reasonably-sized structure in the brain, the sensory relay station that integrates our sensory perceptions- it appears to be the executive leader, overseeing important processes and directing this to go there. Then take the hypothalamus. A tiny, tiny structure beneath the thalamus, shadowed by the size and power of the thalamus. Ordinarily, you’d think the hypothalamus could be nothing more than the thalamus’ shmuck, a secretary or assistant to the highly glorified leader. But boy, could you not be more in the wrong. I’d say the hypothalamus is the king (or queen) of Diencephalon Land, managing not only the brain but the entire body. In what could be considered a behind-the-scenes kind of way, the hypothalamus crucially regulates homeostasis (our temperature, energy levels, stress levels), not to mention the 4 Fs- food, fight, flight, and…say, frivolity in the bed. Ahem. Its name doesn’t give it much credit, to be perfectly honest.

In any case, a recent review paper addressed the hypothalamic regulation of sleep and metabolism, where, perhaps not-so-surprisingly, there’s a link. Sleep and food are two requirements for survival of the species; Maslow’s famous Hierarchy of Needs places them at the very bottom, essential for our well-being. (This could explain why the term “hangry” came about; no one cares about acting ridiculously upset when they need food in their belly.) And, big surprise here, the hypothalamus has a critical role in managing circuitry underlying sleep-wake cycles and metabolism.

We already know from COGS163 that the arcuate nucleus of the hypothalamus contains two populations of neurons: orexigenic (eat!) and anorexigenic (stop eating!). Orexigenic neurons include AgRP and NPY, while anorexigenic neurons include POMC and CART. Appetite and metabolism is regulated through interactions between these populations of neurons and signals from hormones like leptin and ghrelin. Leptin inhibits appetite and increases energy expenditure, while ghrelin increases appetite and decreases energy expenditure via action on these neurons.

These arcuate neurons project to the lateral hypothalamus, which contains “second-order” neurons that produce Hcrt (hypocretin) and MCH (melanin-concentrating hormone). Both of these neuropeptides are involved in the sleep-wake cycle, working cooperatively to provide a “sensor-effector” circuit of arousal.

First, to establish the relationship between sleep and metabolism, the paper explains that sleep duration is inversely correlated with metabolic rate, so the less sleep you get, the higher your metabolic rate. Rodent studies actually showed that depriving mice of sleep increased their activity and stress levels (shocking!). Shorter sleep durations have also been associated with lower leptin and higher ghrelin and glucose levels, corresponding with the possibility that shorter sleep duration and disruptions in the sleep-wake cycle can lead to Type II Diabetes.

When looking at Hcrt specifically, one sees that the peptide promotes wakefulness and arousal. It is close contact with CRF (corticotropin releasing factor), which initiates stress response. Thus, increased stress correlates with increased arousal, explaining why it is indeed hard to sleep when you can’t stop thinking about things that stress you out. Hcrt is also involved in reward pathways associated with feeding, increasing motivation to eat good-tasting foods. Hcrt’s friend, MCH, has undeniably been proven to exert orexigenic effects as well, but instead of increasing energy expenditure, it decreases energy expenditure, dampening metabolism. Thus, the two can have opposite effects: MCH promotes sleep and energy conservation, while Hcrt promotes arousal and energy expenditure, precipitating reward-seeking behaviors.

Thus, the hypothalamus once again proves its superior role in regulating these circuits. Another interesting paper I came across describes the relationship between sleep and the progression of neurodegenerative diseases, such as Alzheimer’s Disease (AD). Right beside the arcuate nucleus and lateral hypothalamus are these spaces called ventricles, which are filled with CSF (cerebrospinal fluid). Proteins linked to neurodegenerative diseases, like amyloid-beta in AD or alpha-synuclein in Parkinson’s Disease, accumulate in interstitial spaces surrounding brain cells, and it’s CSF’s job to remove these proteins via the glymphatic system, a special sort of lymphatic system localized to the brain. Sleep enhances removal of these toxic waste products by CSF. In the study, as much as 65% of exogenously delivered amyloid-beta was cleared by the glymphatic system, cleared twice as fast in sleeping mice than in awake mice. Researchers found that the interstitial space in awake mice is significantly smaller than it is in sleeping mice, so influx of CSF and circulation becomes suppressed as a result of this contraction, preventing CSF from removing the toxic proteins. Thus, they discovered that the sleep-wake state itself is what determines the volume of the interstitial space, not circadian rhythms. Further evidence shows that inhibiting epinenephrine, the neurotransmitter released in stress responses, increases CSF influx in awake mice, demonstrating how stress and arousal are related.

So, this is all fine and dandy, but what does it have to do with us? The simple answer is: get enough sleep. As we all should know, the recommended number of hours of sleep to get for people our age is 6–8 per night, which allows for enough sleep cycles and the REM sleep stage to occur. In REM sleep, we dream- and who doesn’t want to dream? Well, aside from that, the REM stage is also the stage of sleep most correlated with memory consolidation, so it’s valid to say you’ll remember more for an exam if you get a decent amount of sleep before the test than if you pull an all-nighter. And, as explained above, getting enough sleep (and making it regular) will also conserve more energy and could protect against the productive of neurodegenerative disease.

My tip for you if you’re having trouble sleeping? Put away the computer and read a book before sleeping. Or, if that’s too hard to do, listen to some relaxing music or try this thing called ASMR (autonomous sensory meridian response). I think it’s the next best thing after meditation. :)

Citations:

Adamantidis, A. & de Lucea, L. (2008) Sleep and metabolism: shared circuits, new connections. Trends in Endocrinology and Metabolism. 19, 362–370.

Xie, L. et al. (2013) Sleep drives metabolite clearance from the adult brain. SCIENCE. 342, 373–377.