Apnea produces neuronal degeneration in the pons and medulla of guinea pigs

Neurobiol Dis. 2010 Oct;40(1):251-64. doi: 10.1016/j.nbd.2010.05.032. Epub 2010 Jun 8.

Abstract

Obstructive sleep apnea and other sleep-related breathing disorders result in recurrent periods of oxygen deprivation (hypoxia), hypercapnia and an increase in the cellular production of reactive oxygen species (oxidative stress-related injury). Individuals with these disorders suffer from a variety of cellular abnormalities that result in cardiopulmonary dysfunctions, disturbances in sleep and other pathologies. In the present experiment, using an animal model of sleep apnea, we determined that the degeneration of neurons and glia, due to apoptosis, occurs in specific regions of the pons and medulla. Adult guinea pigs, which were divided into control (normoxic) and experimental (hypoxic) groups, were anesthetized with alpha-chloralose and immobilized with Flaxedil. Apnea (hypoxia) was induced by ventilatory arrest in order to desaturate the oxyhemoglobin to 75% SpO(2). A sequence of apnea, followed by ventilation with recovery to >95% SpO(2), was repeated for a period of 3h. At the end of the period of recurrent apnea, the animals were perfused and brain sections were immunostained with a mouse monoclonal antibody raised against single-stranded DNA (ssDNA). Apoptotic neurons and glia, which were not found in the control group of animals, were present in brainstem regions in hypoxic group of animals; these regions involved in the control of respiration (e.g., the parafacial respiratory group and the ventral respiratory group), cardiovascular functions (e.g., the nucleus ambiguus, the nucleus tractus solitarius and the dorsal motor nucleus of the vagus) as well as REM sleep (the nucleus pontis oralis) and wakefulness (e.g., the dorsal raphe and locus ceruleus). We suggest apoptotic neurons and glia in critical areas of the pons and medulla results in many of the comorbidities experienced by patients with sleep-disordered breathing pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Guinea Pigs
  • Hypoxia, Brain / etiology*
  • Hypoxia, Brain / pathology*
  • Medulla Oblongata / pathology
  • Nerve Degeneration / etiology*
  • Nerve Degeneration / pathology*
  • Neuroglia / pathology
  • Neurons / pathology
  • Pons / pathology*
  • Rhombencephalon / pathology*
  • Sleep Apnea Syndromes / complications
  • Sleep Apnea Syndromes / pathology*