Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia

PLoS One. 2017 Jan 6;12(1):e0168430. doi: 10.1371/journal.pone.0168430. eCollection 2017.

Abstract

Study objectives: Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke.

Methods: Sprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR.

Results: A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group.

Conclusions: Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

MeSH terms

  • Animals
  • Electroencephalography
  • Electromyography
  • Gene Expression
  • Hypothalamic Hormones / genetics
  • Hypothalamic Hormones / physiology*
  • Male
  • Melanins / genetics
  • Melanins / physiology*
  • Orexins / genetics
  • Orexins / physiology*
  • Pituitary Hormones / genetics
  • Pituitary Hormones / physiology*
  • Prognosis
  • Rats, Sprague-Dawley
  • Sleep Deprivation*
  • Sleep, REM*
  • Stroke / genetics
  • Stroke / physiopathology*

Substances

  • Hypothalamic Hormones
  • Melanins
  • Orexins
  • Pituitary Hormones
  • melanin-concentrating hormone

Grants and funding

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.