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Narcolepsy as a Disorder of the Hypocretin System

Narcolepsy as a Disorder of the Hypocretin System

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Published by: Vanessa on Aug 03, 2008
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09/06/2012

 
VANESSA VILLAMIA SOCHAT
Narcolepsy as a Disorder of theHypocretin System
How levels of orexins might lead to narcolepsy, & why those levels are off in the first placeThe Neuroscience of Illusions3/27/2008
This paper hypothesizes that narcoleptics might have lower levels of hypocretins that leads to aninability to maintain wakefulness and more sporadic activation of monoaminergic neurons that consequently leads to disturbed sleep. To study this hypothesis, this paper suggests using PET scan tomeasure hypocretin and monamine levels in narcoleptic and normal subjects, and correlate these levelswith state of arousal and REM vs NREM sleep as recorded by EEG during sleep onset, during sleep, and waking. These measurements, in context of one another, might reveal patterns between hypocretinlevels, monoaminergic activity, and how these trends correlate with the perceptual experience of beingawake or asleep. This paper ultimately hypothesizes that narcoleptics will have substantially lower levelsof hypocretins than normals, and as a result, monoaminergic activity might fluctuate more often and rapidly to activate cortex and thalamus, leading to observed changes in arousal.
 
 
CONTENTS
Part I: Narcolepsy as a Disorder of the Hypocretin System ............................................................................ 3
 
Background and Significance
.................................................................................................................... 3
 
Physiology of Sleep Regulation
.............................................................................................................. 3
 
The Hypothalamus as Key Player
........................................................................................................... 4
 
The Hypocretin System
.......................................................................................................................... 4
 
The Hypocretin System and Sleep
......................................................................................................... 4
 
The Hypocretin System and Narcolepsy
................................................................................................ 5
 
Hypocretins are Missing in Narcoleptics
............................................................................................... 5
 
The Reign of the Hypocretin System
..................................................................................................... 6
 
Hypocretins and Arousal
........................................................................................................................ 7
 
Description of a Novel Scientific Problem
..................................................................................................... 8
 
Experimental Synopsis
................................................................................................................................... 8
 
Specific Aims
................................................................................................................................................... 9
 
Future Research:
.................................................................................................................................. 10
 
Part II: The Underlying Cause of Hypocretin Deficit ..................................................................................... 11
 
It Probably isn’t Genes
............................................................................................................................ 11
 
Might it be an Autoimmune Disorder?
................................................................................................... 11
 
Why a lack of compelling evidence?
....................................................................................................... 12
 
Bibliography
………………………………………………………………………………………………………………………………………..14
 
PART I: NARCOLEPSY AS A DISORDER OF THE HYPOCRETIN SYSTEM
BACKGROUND AND SIGNIFICANCE
Much research has been done to assess genetic and biological explanations of narcolepsy andsleep disorder. Although physiological explanations have been made to discuss these phenomena, thecurrent research lacks an analysis of how this physiology leads to the perceptual phenomena associatedwith sleep disorder. Low levels of hypocretins are hypothesized to be responsible for sleep disorder, yetthe cause of these low levels is still unclear. This paper aims to ultimately address the important points of research related to hypocretins, narcolepsy, and perception, and propose that narcolepsy is a disease of the hypocretin system. There is an enormous gap in answering the question about what physical andperceptual disorders these low levels might cause, and as a subtopic, why certain individuals mightpossess low levels of hypocretins in the first place. Making connections between the hypocretin systemand other parts of the brain, this paper ultimately strives to link the hypocretin system to other sleep andneurological disorders and phenomena to influence future research.
Physiology of Sleep Regulation
In order to understand sleep disorder, it is necessary to understand the physiology of normalsleep
.
During REM sleep, skeletal muscles are inhibited by means of the medulla and spinal cord, and thisleads to atonia, which is basically a complete relaxation of all muscles that occurs during sleep. Thesimplest explanation of narcolepsy and other sleep disorder such as paralysis and cataplexy is the idea of REM sleep atonia intruding into a wakeful state accompanied by other perceptual phenomena.It was first hypothesized that these three sleep disorders are a result of hypoactivedopaminagenic transmission, which would explain why many disorders can be alleviated by modulatingdopamine pre-synaptically. Cataplexy, which is often present in individuals with narcolepsy and othersleep disorder, is classified by muscular weakness that ranges from specific groups to the entire body.This is the phenomenon of an individual “falling asleep” with strong emotional stimulation like laughter orsurprise. Cataplexy was found to be related to levels of dopamine. A study using localized injection foundthat inhibitory dopaminergic autoreceptors are linked to cataplexy (Reid et al., 1996).

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