Supplementation with Nicotinamide Riboside Reduces Brain Inflammation and Improves Cognitive Function in Diabetic Mice

Int J Mol Sci. 2019 Aug 27;20(17):4196. doi: 10.3390/ijms20174196.

Abstract

The purpose of this study is to investigate whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. ICR male mice were fed for 14 weeks with either high-fat chow diet (HF, 60% kcal fat) or standard chow diet (CON, 10% kcal fat). HF, streptozotocin, and nicotinamide were used to induce hyperglycemia. NR or vehicle was delivered via stomach gavage for six weeks. Oral glucose tolerance test, Y-maze test, and nest construction test were conducted before and after the NR treatment period. NR treatment induced down-regulation of NLRP3, ASC, and caspase-1. NR reduced IL-1 expression significantly by 50% in whole brains of hyperglycemic mice. Other inflammatory markers including TNF-α and IL-6 were also attenuated by NR. Brain expression of amyloid-β precursor protein and presenilin 1 were reduced by NR. In addition, NR induced significant reduction of amyloid-β in whole brains of diabetic mice. NR treatment restored hyperglycemia-induced increases in brain karyopyknosis to the levels of controls. Nest construction test showed that NR improved hippocampus functions. Spatial recognition memory and locomotor activity were also improved by NR supplementation. These findings suggest that NR may be useful for treating cognitive impairment by inhibiting amyloidogenesis and neuroinflammation.

Keywords: amyloidogenesis; cognitive impairment; neuroinflammation; nicotinamide riboside.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Brain / drug effects*
  • Brain / metabolism
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cognition
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / etiology
  • Diabetes Mellitus, Experimental / complications*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred ICR
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Niacinamide / therapeutic use
  • Pyridinium Compounds
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • CARD Signaling Adaptor Proteins
  • Interleukin-6
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Pycard protein, mouse
  • Pyridinium Compounds
  • Tumor Necrosis Factor-alpha
  • nicotinamide-beta-riboside
  • Niacinamide
  • Caspase 3