Melatonin improves maternal sleep deprivation-induced learning and memory impairment, inflammation, and synaptic dysfunction in murine male adult offspring

Brain Behav. 2024 May;14(5):e3515. doi: 10.1002/brb3.3515.

Abstract

Introduction: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown.

Methods: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting.

Results: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels.

Conclusions: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.

Keywords: cognition; inflammation; maternal sleep deprivation; synaptic proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology
  • Female
  • Hippocampus* / drug effects
  • Hippocampus* / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Maternal Deprivation
  • Melatonin* / administration & dosage
  • Melatonin* / pharmacology
  • Memory Disorders* / drug therapy
  • Memory Disorders* / etiology
  • Memory Disorders* / physiopathology
  • Mice
  • Neuroinflammatory Diseases / drug therapy
  • Neuronal Plasticity* / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Prenatal Exposure Delayed Effects / physiopathology
  • Sleep Deprivation* / complications
  • Sleep Deprivation* / drug therapy
  • Sleep Deprivation* / physiopathology

Substances

  • Melatonin
  • Brain-Derived Neurotrophic Factor