REM Sleep Behavior Disorder in the Marmoset MPTP Model of Early Parkinson Disease

  • Verhave P
  • Jongsma M
  • den Berg R
 et al. 
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Study Objectives: Sleep problems are a common phenomenon in most
neurological and psychiatric diseases. In Parkinson disease (PD), for
instance, sleep problems may be the most common and burdensome non-motor
symptoms in addition to the well-described classical motor symptoms.
Since sleep disturbances generally become apparent in the disease before
motor symptoms emerge, they may represent early diagnostic tools and a
means to investigate early mechanisms in PD onset. The sleep
disturbance, REM sleep behavior disorder (RBD), precedes PD in one-third
of patients. We therefore investigated sleep changes in marmoset monkeys
treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride
(MPTP), the non-human primate model for idiopathic PD.
Design: Mild parkinsonism was induced in 5 marmoset monkeys (3M/2F) over
a 2-week period of subchronic MPTP treatment. Electroencephalograms
(EEGs) and electromyograms (EMGs) were recorded weekly. Motor activity
and hand-eye coordination were also measured weekly, and any signs of
parkinsonism were noted each day. Sleep parameters, motor activity, and
performance data before and after MPTP treatment were compared between
MPTP-treated marmosets and 4 control marmosets (1M/3F).
Results: MPTP increased the number of sleep epochs with high-amplitude
EMG bouts during REM sleep relative to control animals (mean +/- SEM
percentage of REM 58.2 +/- 9.3 vs. 29.6 +/- 7.7; P < 0.05). Of all sleep
parameters measured, RBD-like measures discriminated best between
MPTP-treated and control animals. On the other hand, functional motor
behavior, as measured by hand-eye coordination, was not affected by MPTP
treatment (correct trials MPTP: 23.40 +/- 3.56 vs. control: 36.13 +/-
5.88 correct trials; P = 0.32).
Conclusions: This REM sleep-specific change, in the absence of profound
changes in wake motor behaviors, suggests that the MPTP marmoset model
of PD could be used for further studies into the mechanisms and
treatment of RBD and other sleep disorders in premotor symptom PD.

Author-supplied keywords

  • Parkinson's Disease; marmoset; REM Sleep Behavior

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  • Peternella S Verhave

  • Marjan J Jongsma

  • Roland M den Berg

  • Jose C Vis

  • Raymond A P Vanwersch

  • August B Smit

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