Intermittent fasting attenuates cognitive dysfunction and systemic disease activity in mice with neuropsychiatric systemic lupus erythematosus.

AIMS: Cognitive dysfunction and systemic disease activity are common manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE), a condition that affects a patient's health and quality of life. Clinical and preclinical studies have demonstrated that intermittent fasting (IF) improves health conditions and quality of life. Therefore, we aimed to test whether IF improves cognitive dysfunction and systemic disease activities in mice with NPSLE and to examine the underlying mechanisms.

MAIN

METHODS

NPSLE-prone MRL/lpr mice underwent 8 weeks of alternate-day fasting or ad libitum feeding, followed by behavioral tests to assess cognitive manifestations and biochemical tests to evaluate systemic disease activities.

KEY FINDINGS: IF significantly improved cognitive functionality, decreased blood-brain barrier permeability, and reduced the activation of astrocytes and microglia in the hippocampi of MRL/lpr mice. IF also improved systemic disease activities, including reduced kidney glomerular injury and interstitial inflammation, peripheral blood autoantibody titer, and splenic T lymphocyte contents. Mechanistic studies demonstrated that IF attenuates cognitive dysfunction by facilitating the microglial transition to the M2-like phenotype via the AMPK/PPARγ/NF-κB pathway.

SIGNIFICANCE: Together, observations from this study suggest a potential therapeutic benefit of IF in the treatment of cognitive dysfunction in patients with NPSLE.