Supplementation with Nicotinamide Riboside Reduces Brain Inflammation and Improves Cognitive Function in Diabetic Mice.

Hee Jae Lee,Soo Jin Yang

doi:10.3390/ijms20174196

Hee Jae Lee, Soo Jin Yang

Open Access

https://doi.org/10.3390/ijms20174196

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Abstract

The purpose of this study is to investigate whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. ICR male mice were fed for 14 weeks with either high-fat chow diet (HF, 60% kcal fat) or standard chow diet (CON, 10% kcal fat). HF, streptozotocin, and nicotinamide were used to induce hyperglycemia. NR or vehicle was delivered via stomach gavage for six weeks. Oral glucose tolerance test, Y-maze test, and nest construction test were conducted before and after the NR treatment period. NR treatment induced down-regulation of NLRP3, ASC, and caspase-1. NR reduced IL-1 expression significantly by 50% in whole brains of hyperglycemic mice. Other inflammatory markers including TNF-α and IL-6 were also attenuated by NR. Brain expression of amyloid-β precursor protein and presenilin 1 were reduced by NR. In addition, NR induced significant reduction of amyloid-β in whole brains of diabetic mice. NR treatment restored hyperglycemia-induced increases in brain karyopyknosis to the levels of controls. Nest construction test showed that NR improved hippocampus functions. Spatial recognition memory and locomotor activity were also improved by NR supplementation. These findings suggest that NR may be useful for treating cognitive impairment by inhibiting amyloidogenesis and neuroinflammation.

Highlights

Alzheimer’s disease (AD) is the most common form of dementia
The weights of whole brain were significantly increased by 6 weeks of nicotinamide riboside (NR) treatment, while there were no significant differences in body weight among groups (Table 1)
Male ICR mice were fed with high fat (HF) diet for 14 weeks and injected with STZ and nicotinamide

Summary

Introduction

Alzheimer’s disease (AD) is the most common form of dementia. It impairs cognitive function and performance of daily life. Amyloid-beta is generated by proteolytic cleavage of amyloid-beta precursor protein (APP) with beta- and gamma-secretases [4]. Presenilin (PS) 1, one of core proteins in gamma-secretase complex core, is considered a regulatory component for amyloid beta generation [5,6]. Monomers of amyloid-beta aggregate to form its multimers, subsequently forming amyloid-beta plaque. These formed amyloid beta plaques can disrupt neuronal structure/integrity on deposited areas and lead to neuronal dysfunction [7]. It is abnormally phosphorylated and aggregated, forming neurofibrillary tangle in AD [2,8]

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