Vigilance states in a parkinsonian model, the MPTP mouse

Eur J Neurosci. 2004 Nov;20(9):2474-8. doi: 10.1111/j.1460-9568.2004.03694.x.

Abstract

Sleep disturbances and vigilance disorders are frequently observed in Parkinson's disease. Despite the fact that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse is one of the best-known animal models of Parkinson's disease, sleep analysis has never previously been performed in this system. In the present study, we explored sleep-wakefulness cycles in MPTP-treated mice and compared the results to data from untreated mice. MPTP (25 mg/kg) was injected daily for 5 days. After recovery, polysomnography was recorded over 48 h. Dopaminergic lesions of the substantia nigra and striata were evaluated using immunohistochemical markers. Immunohistochemical analysis showed a loss of dopaminergic neurons in MPTP mice. Compared with controls, MPTP-treated mice presented changes in sleep architecture throughout the nycthemeral period, with longer wakefulness and paradoxical sleep episodes and an increase in the amount of paradoxical sleep. We observed changes in sleep architecture in MPTP-treated mice, compared with saline-treated mice. MPTP mice show more consolidated vigilance states with higher amount of paradoxical sleep than controls. Although the MPTP-treated mouse is not a good model of sleep disturbances in PD, our results suggest that it could be a good pharmacological model for studying the effects of dopaminergic treatments on animal sleep-wakefulness cycles.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Arousal / drug effects
  • Arousal / physiology*
  • Circadian Rhythm / drug effects
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine / pharmacology
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neostriatum / metabolism
  • Neostriatum / pathology
  • Neostriatum / physiopathology
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / physiopathology*
  • Polysomnography
  • Sleep Wake Disorders / etiology
  • Sleep Wake Disorders / pathology
  • Sleep Wake Disorders / physiopathology*
  • Sleep, REM / physiology
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Substantia Nigra / physiopathology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Dopamine