New Fluorescent Orexin Biosensor Aids in Understanding Narcolepsy

According to a recent article, researchers in Europe have created a fluorescent biosensor to look at the signaling molecule orexin in mice brains to help understand narcolepsy.

Narcolepsy

Narcolepsy and excessive daytime sleepiness (EDS) are caused by a neurological disorder that prevents the brain from regulating a person’s sleep-wake cycle. This condition is different from idiopathic hypersomnia. People who have narcolepsy can fall instantly asleep for a few moments, or a few minutes. Some even stay asleep longer and can experience hallucinations while asleep or upon waking. Not all people with narcolepsy experience cataplexy, or the sudden loss of muscle control, but many do. Most people are not diagnosed until years after the onset of symptoms.

Symptoms:

Cataplexy is a unique symptom of narcolepsy that is characterized by sudden and uncontrollable muscle weakness, or paralysis that is generally triggered by a strong emotion, such as excitement, fear, anger, or laughter. Cataplexy by itself is often misdiagnosed as a seizure disorder. Cataplectic attacks vary in severity from slight momentary drooping of the eyelids to the inability to remain standing.

A person experiencing a cataplectic attack usually is awake and aware of what is happening but cannot move. These episodes last up to a few minutes, and some people may fall asleep afterwards. The frequency of cataplectic episodes varies widely among people with narcolepsy.

Orexin

Orexin is a neuropeptide signaling molecule in the brain. Its job is to regulate arousal, wakefulness, motivation, and appetite. Whenever there is a defect pertaining to orexin neuropeptides, it results in narcolepsy.

The Team Behind the Sensor

A team at the University of Zurich, headed by Tommaso Patriarchi, is responsible for the creation of the fluorescent biosensor. The biosensor is encoded to look at orexin’s action and release mechanisms in real time at a high resolution. So far, the device has been used to look at this process in living mice brains.

The Fluorescent Orexin Biosensor

The biosensor has been named OxLight1. It specifically marks the orexin receptor with a fluorescent protein which then enables the receptor to be visible when looking at it under a microscope.

Researchers realized that before they can fully understand how neuropeptides systems act, they needed to first look at the messaging process and understand how it works. Before creating this biosensor, there were no tools that showed this process in real time and with such a good resolution. In creating the biosensor, researchers can now gain this missing insight.

Before using the tool on humans, researchers first need to test it on living mice. From this testing, they were able to discover that the orexin levels released is directly related to the frequency and duration of neuronal activation.

The research team observed the orexin dynamics in sleep and wake transitions. They found that during the mice’s REM sleep, they actually experienced a quick drop in orexin levels. Researchers used this finding and worked with other researchers to look at orexin fluctuations when coming out of anesthesia and understanding the mechanisms of narcolepsy and addiction.

The fluorescent orexin biosensor is now being used across the world to study brain functions.

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