The role of dietary niacin intake and the adenosine-5'-diphosphate-ribosyl cyclase enzyme CD38 in spatial learning ability: is cyclic adenosine diphosphate ribose the link between diet and behaviour?

Nutr Res Rev. 2008 Jun;21(1):42-55. doi: 10.1017/S0954422408945182.


The pyridine nucleotide NAD+ is derived from dietary niacin and serves as the substrate for the synthesis of cyclic ADP-ribose (cADPR), an intracellular Ca signalling molecule that plays an important role in synaptic plasticity in the hippocampus, a region of the brain involved in spatial learning. cADPR is formed in part via the activity of the ADP-ribosyl cyclase enzyme CD38, which is widespread throughout the brain. In the present review, current evidence of the relationship between dietary niacin and behaviour is presented following investigations of the effect of niacin deficiency, pharmacological nicotinamide supplementation and CD38 gene deletion on brain nucleotides and spatial learning ability in mice and rats. In young male rats, both niacin deficiency and nicotinamide supplementation significantly altered brain NAD+ and cADPR, both of which were inversely correlated with spatial learning ability. These results were consistent across three different models of niacin deficiency (pair feeding, partially restricted feeding and niacin recovery). Similar changes in spatial learning ability were observed in Cd38- / - mice, which also showed decreases in brain cADPR. These findings suggest an inverse relationship between spatial learning ability, dietary niacin intake and cADPR, although a direct link between cADPR and spatial learning ability is still missing. Dietary niacin may therefore play a role in the molecular events regulating learning performance, and further investigations of niacin intake, CD38 and cADPR may help identify potential molecular targets for clinical intervention to enhance learning and prevent or reverse cognitive decline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADP-ribosyl Cyclase / administration & dosage*
  • ADP-ribosyl Cyclase / physiology
  • ADP-ribosyl Cyclase 1 / metabolism*
  • Animals
  • Brain / metabolism
  • Cyclic ADP-Ribose / metabolism
  • Diet*
  • Humans
  • Learning
  • Mice
  • Niacin / administration & dosage*
  • Niacin / deficiency
  • Niacin / physiology
  • Rats
  • Spatial Behavior / drug effects*
  • Spatial Behavior / physiology


  • Cyclic ADP-Ribose
  • Niacin
  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1