by Lilian Fennell

My friends and I were out for dinner at my favourite restaurant. The evening was going well and we were having a great……THUMP! A man at the table next to us who had just been quite animatedly telling a joke to his friend was suddenly, well, what looked like asleep? He had knocked over his soup by dropping his spoon uncontrollably into it. There was soup all over the table-cloth yet the man continued to sleep.  A waitress came rushing over to help clean up the soup. Minutes later the man woke up.

Three times during the meal the man nodded off. His friend was watchful of him yet did not seem to worry. My friends and I were puzzled by the man’s sudden need to sleep. He was meant to be out enjoying a meal with his friend.  Surely he was not doing this on purpose…

It turned out the man suffered from narcolepsy which affects 1 in 2000. That’s just under ten people in a college the size of UCC. They are prone to excessive sleep and endure “sleep attacks” throughout the day. Symptoms include cataplexy which is a sudden weakness of the muscles often triggered by strong emotions.

Narcolepsy is thought to be due to a disorder of a specific part of the brain involved in wakefulness called the hypocretin system. These are neuropeptides which are proteins in the brain used by neurons  to communicate with each other. Two of these, known as Hypocretin 1 and Hypocretin 2 (also known as Orexin 1 and 2), are produced in the hypothalamic neurons. They are crucial in deciding whether we need to sleep or be awake. These neuropeptides are responsible for inducing other neurons in the brain to help us stay awake. Narcolepsy results when hypocretin is deficient in the brain.

Our restful winks come in two forms: non-rapid eye movement (NREM) sleep which is also known as “quiet sleep” and rapid eye movement (REM) sleep which is also known as “active sleep”.  Even though a person is asleep, if they are in the REM state, their brain is still highly active so this state of sleep is restoring for the body, but the brain is still alert. In this state,  you are most likely to dream. During NREM state, the body is both mentally and physically restored and the brain is not as active.

With narcolepsy, both quiet and active sleep are greatly disrupted and the narcoleptic individual is prone to rapid and sudden transitions between being in a state of wakefulness to suddenly dropping their spoon and startling the surrounding diners. Individuals who suffer from narcolepsy often continue to do the tasks they were doing while awake, for example washing the dishes, while remaining asleep.

Narcolepsy is thought to be associated with the HLA-DQB1 gene. This gene contains instructions to make a protein that plays an important role in the immune system. This protein allows the immune system to identify the body’s own proteins (self) as well as foreign proteins made by viruses and bacteria (non-self) and signals their destruction. One version of this gene, increases the risk of narcolepsy, especially in those who already suffer from cataplexy alone.

Recent work has shown that narcolepsy may be truly related to a dysfunction of the immune system.  In 2010, scientists found that an overproduction of antibodies specific to the oddly named ‘Tribbles homolog 2 protein’ was a characteristic of narcolepsy patients. These antibodies may help in aiding the development of narcolepsy by causing the neurons which make hypocretin to rapidly degenerate.

Currently there is no cure for disorders of sleep such as narcolepsy as we do not fully understand all aspects of them as yet. Only lifestyle changes can help people who suffer from these. Clearly, the order and disorder of sleep is still a mystery to humans but research is ongoing and reaping many successes. A critical understanding of it will help us improve our quality of sleep as well as helping those who lack it. It might cut down on dry cleaning costs too!

Lilian Fennell is currently studying for a Masters in Molecular Cell Biology with Bioinnovation at University College Cork and is an eager communicator and blogger of science

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References:

Hor, Hyun. (2010) Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nature Genetics, 42(9), 786-789. DOI: 10.1038/ng.647

Sakurai, Takeshi. (2007) The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nature Reviews Neuroscience, 8(3), 171-181. DOI: 10.1038/nrn2092

Schwartz, Jonathan. (2008) Neurophysiology of Sleep and Wakefulness: Basic Science and Clinical Implications. Current Neuropharmacology, 6(4), 367-378. DOI: 10.2174/157015908787386050

Takahashi, Joseph S. (2008) The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nature Reviews Genetics, 9(10), 764-775. DOI: 10.1038/nrg2430

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