Targeting sirtuin activity with nicotinamide riboside reduces neuroinflammation in a GWI mouse model.

Targeting sirtuin activity with nicotinamide riboside reduces neuroinflammation in a GWI mouse model. Neurotoxicology. 2020 Apr 25;: Authors: Joshi U, Evans JE, Pearson A, Saltiel N, Cseresznye A, Darcey T, Ojo J, Keegan AP, Oberlin S, Mouzon B, Paris D, Klimas N, Sullivan K, Mullan M, Crawford F, Abdullah L Abstract Gulf War Illness (GWI) affects 30% of veterans from the 1991 Gulf War (GW), who suffer from symptoms that reflect ongoing mitochondria dysfunction. Brain mitochondria bioenergetics dysfunction in GWI animal models corresponds with astroglia activation and neuroinflammation. In a pilot study of GW veterans (n = 43), we observed that blood nicotinamide adenine dinucleotide (NAD) and sirtuin 1 (Sirt1) protein levels were decreased in the blood of veterans with GWI compared to healthy GW veterans. Since nicotinamide riboside (NR)-mediated targeting of Sirt1 is shown to improve mitochondria function, we tested whether NR can restore brain bioenergetics and reduce neuroinflammation in a GWI mouse model. We administered a mouse diet supplemented with NR at 100μg/kg daily for 2-months to GWI and control mice (n = 27). During treatment, mice were assessed for fatigue-type behavior using the Forced Swim Test (FST), followed by euthanasia for biochemistry and immunohistochemistry analyses. Fatigue-type behavior was elevated in GWI mice compared to control mice and lower in GWI mice treated with NR compared to untreated GWI...
Source: Neurotoxicology - Category: Neurology Authors: Tags: Neurotoxicology Source Type: research