Sleep (Part 1) - Neurochemical Tapestry



Sleep,



A seemingly passive state, yet a world of vibrant complexity.


A dreamscape far more intricate than we realize.




Forget bending spoons... In sleep, your mind bends reality, right?


The science of sleep reveals how our minds shape the very fabric of our rest.




This blog series invites you to explore the fascinating world of sleep.


The boundaries between dreams and reality may be more blurred than we ever knew..



Let’s begin.




Section 1: Key Players in the Neurochemical Symphony

What makes you YOU?



Is it the flash of a thought, a surge of emotion, or the predictable rhythm of your days?



According to science, the answer lies within your brain

An endless network of neurons hums with activity,

Exchanging information crucial to your very existence.



This communication involves electrical signals and chemical messengersneurotransmitters and hormones.

These molecules dictate our natural cycles of sleep and wakefulness.


Melatonin (hormone)— Conductor of Our Nighttime Rhythm

Nestled deep within the brain, the pineal gland directs the production of melatonin .

Melatonin is a hormone linked to our circadian rhythm

The internal 24-hour clock that governs our sleep-wake cycle (Reiter et al., 1995).


Neurochemical Symphony

When dark, the pineal gland receives cues from light-sensitive cells in the eyes. 

In response, melatonin production increases, and signals to the body to prepare for sleep


Physiological Changes

Natural dip in body temperature

Feeling of drowsiness

Increased production of the sleep hormone adenosine



Disruptions to the Symphony

Exposure to artificial light (blue light) disrupts melatonin production.

Likely why those late-night social media scrolls can significantly hinder your ability to fall asleep.


Adenosine (neurotransmitter)— The Gauge of Sleep Pressure

A chemical called adenosine accumulates in the brain as we remain awake(Porkka-Heiskanen, 1999).

Adenosine acts like a gauge of “sleep pressure, increasing with our waking duration,

Accumulation of adenosine increases drowsiness as the day progresses.


Neurochemical Symphony

Neurons don’t produce Adenosine.

Adenosine is a byproduct of cellular energy use (ATP)

Think of it as a metabolic byproduct that builds up as our brain cells burn fuel throughout the day. 


Physiological Changes

Gradual decrease in alertness

Increased cognitive fog

Growing desire for sleep

Decreased reaction times and physical coordination.


Cortisol (hormone): Stress and the Disrupted Rhythm



The primary stress hormone cortisol was covered in our blog post—

Stress Escape: Finding Calm Beyond the Matrix


Cortisol naturally fluctuates throughout the day (Leproult et al., 1997)—

Highest in the morning, declines throughout the day,

Promotes relaxation and sleep onset in the evening.

Neurochemical Symphony

When we are stressed, hypothalamic-pituitary-adrenal (HPA) axis is activated, triggering the release of cortisol.

This is a vital response designed to help us cope with stressful situations.

Physiological Changes

Chronic stress disrupts the natural cortisol rhythm.

Persistently high cortisol levels in the evening can cause—

Difficulty falling asleep (sleep-onset insomnia)

Difficulty staying asleep (sleep-maintenance insomnia)

Racing thoughts

Anxiety

GABA(Neurotransmitter): Brain’s Natural Tranquilizer

Gamma-aminobutyric acid (GABA) is the brain's primary inhibitory neurotransmitter—

Like a dimmer switch that reduces the overall activity of neurons.

GABA plays a crucial role in (Gottesmann, 2002),

Reducing anxiety

Promoting calmness

Facilitating transition into sleep

Neurochemical Symphony

GABA is synthesized from glutamate—another neurotransmitter involved in excitation.

Maintaining a balance between GABA and glutamate is key for healthy brain function.

Several medications and supplements target this GABA system to treat sleep and anxiety issues.

Physiological Changes

Lower brain activity

Reduced heart rate

Relaxed muscles

Counters the effects of stress hormones (like cortisol)

Creates a physiological environment conducive to sleep


The Interplay of Neurochemicals:

Beyond GABA and Cortisol



While cortisol and GABA play significant roles in sleep, they are NOT the only players—

1. Other Neurotransmitters

Neurotransmitters like serotonin and dopamine interact with sleep-wake regulation pathways.

These systems can influence mood, alertness, and the timing of our circadian rhythm.



2. Neuromodulators

Substances like orexin (hypocretin) promotes wakefulness.

Disruptions in the orexin system are implicated in sleep disorders like narcolepsy (De Lecea, 2019).

More on this later..



3. Sleep-Promoting Substances

Remember, Adenosine is produced throughout the day, building up the "sleep pressure."


Practical Implications: Supporting Optimal GABA Function

While research is ongoing, some strategies may support GABA function and better sleep—

1. Stress Management Techniques

Practices like yoga, mindfulness, and meditation lowers cortisol levels while promoting GABA activity.


2. Regular Exercise

Physical activity can help reduce stress, improve mood, and potentially enhance GABA production.



3. Nutrition and Supplements

Do your research before considering supplements that claim to target GABA receptors (i.e. Herbs or amino acids).

It's crucial to remember that more research is needed to fully understand their effectiveness and safety.

  

In Pharmer's Lab, we published a personal trial review for a PharmaGABA supplement (No affiliations to disclose).

Click here for more.

GABA Reference Studies (FYI)


What's Next?


We've seen the overall blueprint of sleep, but now it's time for a close-up tour.

Each stage – NREM 1,2,3 and even REM – has its own unique quirks and secrets to unlock.

I'll meet you in the next stage of our journey.

Moose, Cat


References

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  2. Arnulf, I., Konofal, E., Gibson, K. M., Rabier, D., Beauvais, P., Derenne, J. P., & Philippe, A. (2005). Effect of genetically caused excess of brain gamma-hydroxybutyric acid and GABA on sleep. Sleep, 28(4), 418–424. https://doi.org/10.1093/sleep/28.4.418

  3. Beersma, D. G., Dijk, D. J., Blok, C. G., & Everhardus, I. (1990). REM sleep deprivation during 5 hours leads to an immediate REM sleep rebound and to suppression of non-REM sleep intensity. Electroencephalography and clinical neurophysiology, 76(2), 114–122. https://doi.org/10.1016/0013-4694(90)90209-3

  4. Gottesmann C. (2002). GABA mechanisms and sleep. Neuroscience, 111(2), 231–239. https://doi.org/10.1016/s0306-4522(02)00034-9

  5. Hepsomali, P., Groeger, J. A., Nishihira, J., & Scholey, A. (2020). Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Frontiers in neuroscience, 14, 923. https://doi.org/10.3389/fnins.2020.00923

  6. Kayabekir, M. (2022). Neurophysiology of Basic Molecules Affecting Sleep and Wakefulness Mechanisms, Fundamentals of Sleep Pharmacology. https://doi:10.5772/intechopen.100166

  7. Leproult, R., Copinschi, G., Buxton, O., & Van Cauter, E. (1997). Sleep loss results in an elevation of cortisol levels the next evening. Sleep, 20(10), 865–870. https://doi.org/10.1093/sleep/20.10.865

  8. Maguire J. (2014). Stress-induced plasticity of GABAergic inhibition. Frontiers in cellular neuroscience, 8, 157. https://doi.org/10.3389/fncel.2014.00157Porkka-Heiskanen, T. (1999). Adenosine in sleep and wakefulness. Annals of Medicine, 31(2), 125-129. https://doi.org/10.3109/07853899908998795

  9. Pace-Schott, E. F., & Hobson, J. A. (2002). The neurobiology of sleep: Genetics, cellular physiology and subcortical networks. Nature Reviews Neuroscience, 3(8), 591-605. https://doi.org/10.1038/nrn895

  10. Reiter, R. J., Tan, D. X., & Fuentes-Broto, L. (2010). Melatonin: A multitasking molecule. Progress in Brain Research. https://doi.org/10.1016/B978-0-444-53607-8.00008-3

  11. Saper, C. B., Scammell, T. E., & Lu, J. (2005). Hypothalamic regulation of sleep and circadian rhythms. Nature, 437(7063), 1257-1263. https://doi.org/10.1038/nature04284

  12. Shen, Y. C., Sun, X., Li, L., Zhang, H. Y., Huang, Z. L., & Wang, Y. Q. (2022). Roles of Neuropeptides in Sleep-Wake Regulation. International journal of molecular sciences, 23(9), 4599. https://doi.org/10.3390/ijms23094599

  13. Siegel J. M. (2005). Clues to the functions of mammalian sleep. Nature, 437(7063), 1264–1271. https://doi.org/10.1038/nature04285

  14. Siegel, J. M. (2009). Sleep viewed as a state of adaptive inactivity. Nature Reviews Neuroscience, 10(10), 747-753. https://doi.org/10.1038/nrn2697

  15. Stickgold, R. (2005). Sleep-dependent memory consolidation. Nature, 437(7063), 1272-1278. https://doi.org/10.1038/nature04286

  16. Walker, M. P., & Stickgold, R. (2006). Sleep, memory, and plasticity. Annual Review of Psychology, 57, 139-166. https://doi.org/10.1146/annurev.psych.56.091103.070307

  17. Yoto, A., Murao, S., Motoki, M., Yokoyama, Y., Horie, N., Takeshima, K., Masuda, K., Kim, M., & Yokogoshi, H. (2012). Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino acids, 43(3), 1331–1337. https://doi.org/10.1007/s00726-011-1206-6


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Sleep (Part 2) - Architecture and Stages

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The Quiet Revolution: Find Peace in Nature Amidst the Digital Chaos