Treatment with reduced nicotinamide adenine dinucleotide (NADH) improves water maze performance in old Wistar rats

Age-associated cognitive impairment and related neurodegenerative disorders are an increasing major public health problem. Nicotinamide adenine dinucleotide (NADH), a co-substrate for energy transfer in the mitochondrial respiratory chain, is speculated to induce positive effects in some of these diseases. Studies showed diminished mitochondrial function in patients with M. Alzheimer. In a preliminary clinical trial NADH given peripherally improved cognitive function in Alzheimer disease. Previous own experiments revealed an increased NADH level in the rat brain following peripheral application of NADH (10-100 mg/kg, i.p.+ i.v.). Therefore, we wanted to know, whether or not NADH has an effect on cognitive function in animals. We analysed the effect of repeated i.p. injection of NADH on the performance of 3-month-old and 22-month-old Wistar rats in the Morris water maze and in the rota-rod test of motor coordination. The rats were injected for 10 days once daily with the doses of NADH used in the bioavailability study (10-100 mg/kg) or vehicle 20 min before the behavioural tests. The repeated administration of NADH improved the performance of old rats in the acquisition phase (place version) and the spatial probe of the Morris water maze compared to vehicle-treated controls. The effect of NADH on learning-related processes is supported by the lack of effects on motor performance on the rota-rod. In summary, our results suggest cognitive enhancing properties of NADH in learning impaired old rats.