Early administration of nicotinamide prevents learning and memory impairment in mice induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine.
OBJECTIVE
NAD has been reported to improve the dementia of the Alzheimer type or sensory register, short- and long-term memory loss in the aged. Although nicotinamide has been confirmed to decrease infarct volumes and neurological deficit findings in several animal stroke models, it is not clear whether its neuroprotective effects can prevent memory damage sequelae.


METHODS
We have addressed this topic by designing two behavioral paradigms. A memory impairment and cognitive change model was used in mice following 1-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine (MPTP) exposure. Step-down and step-through tests were performed to examine the effects of nicotinamide on learning and memory impairment.


RESULTS
It was found that the early administration of nicotinamide (2 h after the injection of MPTP) could decrease error numbers, lessen stimulation time and prolong residence duration on the safety platform in the step-down test. Delayed administration of nicotinamide resulted in decreased effects. Similar results were found in the step-through test. Nicotinamide administrated 12 h after the induction of a memory-impairment model still exerted its effects on memory dysfunction.


CONCLUSIONS
The injection of MPTP can cause a loss of brain functions including learning and memory. Learning and memory dysfunction probably occurs secondary to damage to arterioles and dopaminergic neurons by MPTP. By inhibiting oxidative stress, increasing NAD synthesis and ATP production and inhibiting poly (ADP-ribose) polymerase, nicotinamide is known to rescue the still viable, but injured, cells. This rescue process may partially restore learning and memory.
Yang
Jun
J
School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
He
Lina
L
Wang
Jing
J
Adams
James D
JD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D051379:Mice; D009536:Niacinamide / Q000008:administration & dosage*
D009536:Niacinamide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine