Chronic Toxoplasma gondii infection and sleep-wake alterations in mice

CNS Neurosci Ther. 2021 Aug;27(8):895-907. doi: 10.1111/cns.13650. Epub 2021 Jun 4.

Abstract

Aim: Toxoplasma gondii (Tg) is an intracellular parasite infecting more than a third of the human population. Yet, the impact of Tg infection on sleep, a highly sensitive index of brain functions, remains unknown. We designed an experimental mouse model of chronic Tg infection to assess the effects on sleep-wake states.

Methods: Mice were infected using cysts of the type II Prugniaud strain. We performed chronic sleep-wake recordings and monitoring as well as EEG power spectral density analysis in order to assess the quantitative and qualitative changes of sleep-wake states. Pharmacological approach was combined to evaluate the direct impact of the infection and inflammation caused by Tg.

Results: Infected mouse exhibited chronic sleep-wake alterations over months, characterized by a marked increase (>20%) in time spent awake and in cortical EEG θ power density of all sleep-wake states. Meanwhile, slow-wave sleep decreased significantly. These effects were alleviated by an anti-inflammatory treatment using corticosteroid dexamethasone.

Conclusion: We demonstrated for the first time the direct consequences of Tg infection on sleep-wake states. The persistently increased wakefulness and reduced sleep fit with the parasite's strategy to enhance dissemination through host predation and are of significance in understanding the neurodegenerative and neuropsychiatric disorders reported in infected patients.

Keywords: Toxoplasma; infection; neuropsychiatric disorders; sleep; wakefulness.

MeSH terms

  • Animals
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Electroencephalography / drug effects
  • Electroencephalography / methods
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Male
  • Mice
  • Mice, Inbred CBA
  • Sleep / drug effects
  • Sleep / physiology
  • Sleep Stages / drug effects
  • Sleep Stages / physiology*
  • Toxoplasmosis / drug therapy
  • Toxoplasmosis / physiopathology*
  • Wakefulness / drug effects
  • Wakefulness / physiology*

Substances

  • Glucocorticoids
  • Dexamethasone