The effect of nicotinamide riboside on cognitive and behavioral symptoms in alzheimer's disease animal model and its relation with mitophagy

Neuropsychiatric symptoms in Alzheimer's disease (AD) are challenging for both caregivers and patients. Depression as one of the neuropsychiatric symptoms of AD, differs from major depression in terms of both clinical features and response to treatment. Antidepressants do not show the expected benefit in the treatment of depression accompanying cognitive symptoms in Alzheimer's patients, thus the mechanism of depressive symptoms in Alzheimer's disease are thought to differ from other depression syndromes. Therefore, studies to explain the pathophysiology of the disease have gained importance. Mitochondrial dsyfunction is thought to play a critical role in the development and maintenance of Alzheimer's disease. In many studies impairment in mitophagy, the selective elimination of damaged mitochondria, has been reported. Studies have shown that inducing mitophagy by increasing nicotinamide adenine dinucleotide (NAD+) reduces amyloid β (Aβ) aggregation and improves cognitive dysfunction in animal models of AD, but there is no data about its' effect on depression observed in AD. The aim of the present study was to investigate the effect of the NAD+ precursor NR on cognitive and neuropsychiatric symptoms in single dose intracerebroventricular (ICV) Aβ1-42 injected rat model of AD. In this AD model, rats showed depression-like behaviors similar to neuropsychiatric symptoms in addition to memory impairment. Rats treated with 700 mg/kg NR via orogastric gavage for 23 days, had better memory performance, less depressive like behavior and lower aggression scores, and slower weight gain rate compared to the no treatment (Aβ+saline) group. This study has shown that the NAD+ precursor NR is effective in the treatment of neuropsychiatric symptoms as well as cognitive deterioration in an Alzheimer's disease model. Keywords: Alzheimer's Disease, Neuropsychiatric symptoms, Mitophagy, NAD, Nicotinamide riboside