What is Hypocretin?

Hypocretin is a neuropeptide used to transmit information between brain cells. The neurotransmitters hypocretin receptor type 1 and hypocretin receptor type 2 play an important role in the regulation of sleep cycles. Increased levels of this neurotransmitter may cause an increase in appetite. Low or nonexistent levels of these hormones are found in people with narcolepsy, a condition that causes excessive daytime sleepiness.

The peptide hypocretin is also known as orexin. Both terms may be used interchangeably in medical nomenclature. The term hypocretin is generally used when referencing sleep cycles, and orexin is more likely to be used when referring to appetite.

Less than 20,000 cells in the brain are able to produce this sleep-regulating hormone. The hypothalamus secretes molecules of this peptide neurotransmitter into the fluid around the brain and spinal cord. These molecules are not diffused into the surrounding tissues or the bloodstream. Blood tests are unable to reveal if the levels of this hormone are within normal limits.

Testing of hypocretin-1 levels is done through a lumbar spinal tap. A long needle is inserted into the spinal cord between the third and fourth vertebrae, and a small amount of cerebrospinal fluid (CSF) is aspirated into a syringe. The fluid is sent to a laboratory to analyze the concentration of the neurotransmitter. Test results may indicate a need for a sleep study to confirm a diagnosis of narcolepsy.

Side effects of the lumbar puncture are considered mild. Many people report a severe headache and lower backache within three days of the procedure. The headache pain is usually greater towards the front of the head or at the base of the skull. Over-the-counter pain relievers may be used to reduce pain. Some doctors may try to prevent the headache by flushing the aspiration site with saline after the CSF sample has been collected.

The spinal tap procedure rarely has serious complications. Nerve damage is possible from the insertion of the needle into the spinal column. This damage could result in a loss of sensation or paralysis in the lower half of the body.

Medication is usually prescribed to treat the symptoms of a hypocretin-1 deficiency. These medicines are not a synthetic form of the missing neurotransmitter. Most people with narcolepsy are prescribed modafinil to promote wakefulness. The medicine acts on the anterior portion of the hypothalamus, the same part of the brain that produces hypocretin. Modafinil prevents the reuptake of the neurotransmitter noradrenaline, resulting in an improved mood and an increased feeling of alertness.