Vitamin C alleviates LPS-induced cognitive impairment in mice by suppressing neuroinflammation and oxidative stress

Int Immunopharmacol. 2018 Dec:65:438-447. doi: 10.1016/j.intimp.2018.10.020. Epub 2018 Oct 30.

Abstract

Neuroinflammation is believed to be one of the primary causes of cognitive impairment. Previous studies showed that the antioxidant vitamin C (Vit C) performs many beneficial functions such as immunostimulant and anti-inflammatory actions, but its role in inflammatory cognitive impairment is unclear. In the current study, we investigated the effect and possible mechanism of action of Vit C in lipopolysaccharide (LPS)-induced cognitive impairment. Intracerebroventricular LPS-induced memory impairment was used as the model for neuroinflammatory cognitive dysfunction. Vit C was administered by intracerebroventricular microinjection 30 min prior to LPS exposure. It was found that Vit C significantly protected animals from LPS-induced memory impairment as evidenced by improved performance in the Morris water maze and novel object recognition tests without changes in spontaneous locomotor activity. Vit C pretreatment inhibited the activation of microglia and the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, Vit C pretreatment markedly decreased the malondialdehyde (MDA) level, increased superoxide dismutase (SOD) activity, and modulated the Bax/Bcl-2 ratio and p-p38 MAPK activation in the hippocampus of LPS-treated mice. Together, these results suggest that vitamin C pretreatment could protect mice from LPS-induced cognitive impairment, possibly through the modulation of oxidative stress and inflammatory responses.

Keywords: Apoptosis; Memory impairment; Neuroinflammation; Oxidative stress; Vitamin C.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Ascorbic Acid / therapeutic use*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Lipopolysaccharides / immunology
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning
  • Memory Disorders / drug therapy*
  • Memory Disorders / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neurogenic Inflammation / drug therapy*
  • Neurogenic Inflammation / immunology
  • Oxidative Stress / drug effects
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • Malondialdehyde
  • p38 Mitogen-Activated Protein Kinases
  • Ascorbic Acid