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Modafinil Reduces Neuronal Pyroptosis and Cognitive Decline After Sleep Deprivation

Xiangyang Xiong1, Yan Zuo1, Lu Cheng1

  • 1Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.

Frontiers in Neuroscience
|March 21, 2022
PubMed

Insights

Modafinil, an antioxidant, combats sleep deprivation-induced neuronal pyroptosis and cognitive decline by reducing inflammation and enhancing synaptic activity in mice.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Sleep deprivation (SD) triggers systemic inflammation, which can lead to neuronal pyroptosis.
  • Neuronal pyroptosis is implicated in cognitive deficits associated with sleep disturbances.

Purpose of the Study:

  • To evaluate the neuroprotective effects of the antioxidant modafinil against neuronal pyroptosis and cognitive impairment induced by sleep deprivation.
  • To elucidate the molecular mechanisms underlying modafinil's action in a mouse model.

Main Methods:

  • A mouse model was utilized to induce sleep deprivation.
  • Modafinil was administered to assess its impact on cognitive functions (learning and memory).
  • Inflammatory markers (IL-1β, TNF-α, IL-6, IL-10), inflammasome activity, and neuronal pyroptosis pathways (NLRP3/NLRP1/NLRC4-caspase-1-IL-1β) were analyzed.

Main Results:

  • Modafinil significantly improved learning and memory in sleep-deprived mice.
  • Treatment with modafinil reduced the production of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and increased anti-inflammatory cytokine (IL-10) expression.
  • Modafinil attenuated inflammasome activation, thereby reducing neuronal pyroptosis and upregulating brain-derived neurotrophic factor (BDNF) and synaptic activity.

Conclusions:

  • Modafinil demonstrates efficacy in mitigating neuronal pyroptosis and cognitive decline resulting from sleep deprivation.
  • The findings suggest modafinil's potential therapeutic value for sleep disorders characterized by inflammation and cognitive impairment.
Keywords:
inflammasomemodafinilpyroptosissleep deprivationsynaptic plasticity

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