“Educating people about just how real this disorder is and how it's not just being tired is crucial.” – Scott

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Advancements in the understanding of narcolepsy are happening. Be the first to know.

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The Role of Histamine in Sleep and Wakefulness

The hypothalamus contains multiple neuronal systems that help promote and stabilize wakefulness.1-3

In the CNS, histamine neurons originate only in the hypothalamic tuberomammillary nucleus (TMN) and project widely throughout the brain to activate neurons in the cortex, thalamus, and other regions outside of the hypothalamus containing wake-promoting neurons (e.g., norepinephrine, acetylcholine, serotonin neurons).2,4 In vivo and in vitro animal studies have shown that histamine neurons also inhibit non-REM sleep– and REM sleep–promoting neurons, helping to stabilize wakefulness during the day.2,4,5,6

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Watch to learn about the role of histamine in regulating sleep and wakefulness.1,2,4-6

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Thomas Scammell, MD from Beth Israel Deaconess Medical Center, Boston Children's Hospital, and Harvard Medical School, discusses key data from several animal studies that support why histamine plays an important role in disorders characterized by sleep-wake state instability, such as narcolepsy.1,4

The Role of Histamine in Narcolepsy

Exploring Histamine in Sleep-Wake State Stability

Signs and symptoms of narcolepsy are not always obvious.

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Narcolepsy symptoms can have a significant impact on people living with the disorder.

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  1. España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-858.
  2. Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
  3. Schwartz JR, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6(4):367-378.
  4. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
  5. Parmentier R, Ohtsu H, Djebbara-Hannas Z, Valatx JL, Watanabe T, Lin JS. Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J Neurosci. 2002;22(17):7695-7711.
  6. Williams RH, Chee MJ, Kroeger D. Optogenetic-mediated release of histamine reveals distal and autoregulatory mechanisms for controlling arousal. J Neurosci. 2014;34(17):6023-6029.

Performance of routine tasks without awareness.

Sudden and brief loss of muscle strength or tone, often triggered by strong emotions. Narcolepsy with cataplexy is known as type 1 narcolepsy.

Complete collapse to the ground; all skeletal muscles are involved.

Only certain muscle groups are involved.

Biological clock mechanism that regulates the 24-hour cycle in the physiological processes of living beings. It is controlled in part by the SCN in the hypothalamus and is affected by the daily light-dark cycle.

Frequent inappropriate transitions between states of sleep and wakefulness.

The inability to stay awake and alert during the day.

A neurotransmitter that supports wakefulness. The TMN is the only source of histamine in the brain.

Vivid, realistic, and frightening dream-like events that occur when falling asleep.

A neuropeptide that supports wakefulness and helps control non-REM sleep and REM sleep.

Primary brain region for regulating the timing of sleep-wake states.

Unintentionally falling asleep due to excessive daytime sleepiness.

Brief, unintentional lapses into sleep or loss of awareness.

A validated objective measure of the tendency to fall asleep in quiet situations.

A state of sleep when muscle tone is decreased. Deep stages help to restore the body.

Overnight study used to diagnose sleep disorders by monitoring sleep stages and cycles to detect disruptions of a normal sleep pattern.

Normally occurs at night and includes vivid dreams. Also known as “paradoxical sleep.”

Daytime and evening habits and routines to help improve nighttime sleep.

Brief loss of control of voluntary muscles with retained awareness.

Sleep-onset REM period.

People with type 1 narcolepsy have low levels of hypocretin.

Narcolepsy without cataplexy; the cause of type 2 narcolepsy is unknown.