European Psychiatry (Apr 2024)
Nicotinamide Riboside Attenuates Memory Impairment and Depressive-like Behavior in an Alzheimer’s Disease Animal Model
Abstract
Introduction Depression in Alzheimer’s disease (AD) differs from major depression in terms of clinical features and treatment. Antidepressants do not provide the expected benefits in depressive symptoms accompanying cognitive decline in AD, suggesting distinct mechanisms. Emerging research suggest that compromised mitophagy, the selective removal of damaged mitochondria, may contribute to the pathogenesis of AD. However boosting nicotinamide adenine dinucleotide (NAD+) to induce mitophagy reduces amyloid β (Aβ) aggregation and enhances cognitive function in AD models (Kerr et al.,Trends Neurosci 2017;40:151-66). Nevertheless, data on NAD’s impact on depression in AD remains limited. Objectives This study aimed to examine the impact of the NAD+ precursor nicotinamide riboside (NR) on cognitive and neuropsychiatric symptoms in a AD rat model. Methods To induce the AD, a single dose of 5 μl Aβ1-42 was injected into each lateral ventricle of rats (day 0), while the control group received an intracerebroventricular (icv) saline (0.9%NaCl).Four experimental groups were designed: control (icv saline+po saline), NR (icv saline+po NR), Aβ (icv Aβ+po saline), and Aβ+NR (icv Aβ+po NR).After the injection, to reduce Aβ clearance (Kang et al. Science. 2009;32 1005-7.) rats were subjected to 96 hours of sleep deprivation.Starting from day 6, rats were given either 700 mg/kg oral NR or saline, and handling test scores were recorded daily.The procedures were repeated daily until the rats were sacrificed on day 28.Behavioral experiments were randomly conducted at the end, and statistical analysis was performed using repeated measures ANOVA, followed by the Tukey post hoc test. Results Passive avoidance test results showed that the Aβ group had the shortest latency to enter the dark area. However, the Aβ+NR group exhibited a prolonged latency compared to the Aβ group (F(3,2)=5.5;p0.05). During the 28-day monitoring period, the Aβ+NR group of rats exhibited a more rapid decrease in aggression levels compared to the other groups in the handling test. This decrease was significant between days 7 and 10 compared to the Aβ group (F(48,5)=1.5;p<0.05). Conclusions NR improved memory, reduced depressive behavior, and lowered aggression in AD rats. This suggests that NAD+ precursor NR effectively treats cognitive decline and neuropsychiatric symptoms in an AD model. Disclosure of Interest None Declared