Nicotinamide Prevents Diabetic Brain Inflammation via NAD+-Dependent Deacetylation Mechanisms
Torres-Méndez, Jeimy Katherine (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Niño-Narvión, J. (Universidad de Murcia (UMU))
Martinez-Santos, Patricia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Diarte-Añazco, E. M. G (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Méndez Lara, Karen Alejandra (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
del Olmo, Tania V. (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Rotllan, Noemi (Institut d'Investigació Biomèdica Sant Pau)
Julián, María Teresa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Alonso Pedrol, Núria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Mauricio, D. (Universitat de Vic)
Camacho, Mercedes (Institut d'Investigació Biomèdica Sant Pau)
Muñoz, Juan Pablo (Institut d'Investigació Biomèdica Sant Pau)
Rossell, Joana (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Julve i Gil, Josep (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	This study investigated the effect of nicotinamide (NAM) supplementation on the development of brain inflammation and microglial activation in a mouse model of type 1 diabetes mellitus. C57BL/6J male mice, which were made diabetic with five consecutive, low-dose (55 mg/kg i. p. ) streptozotocin (STZ) injections. Diabetic mice were randomly distributed in different experimental groups and challenged to different doses of NAM (untreated, NAM low-dose, LD, 0. 1%; NAM high-dose, HD, 0. 25%) for 25 days. A control, non-diabetic group of mice was used as a reference. The NAD+ content was increased in the brains of NAM-treated mice compared with untreated diabetic mice (NAM LD: 3-fold; NAM HD: 3-fold, p-value < 0. 05). Immunohistochemical staining revealed that markers of inflammation (TNFα: NAM LD: −35%; NAM HD: −46%; p-value < 0. 05) and microglial activation (IBA-1: NAM LD: −29%; NAM HD: −50%; p-value < 0. 05; BDKRB1: NAM LD: −36%; NAM HD: −37%; p-value < 0. 05) in brains from NAM-treated diabetic mice were significantly decreased compared with non-treated T1D mice. This finding was accompanied by a concomitant alleviation of nuclear NFκB (p65) signaling in treated diabetic mice (NFκB (p65): NAM LD: −38%; NAM HD: −53%, p-value < 0. 05). Notably, the acetylated form of the nuclear NFκB (p65) was significantly decreased in the brains of NAM-treated, diabetic mice (NAM LD: −48%; NAM HD: −63%, p-value < 0. 05) and inversely correlated with NAD+ content (r = −0. 50, p-value = 0. 03), suggesting increased activity of NAD+-dependent deacetylases in the brains of treated mice. Thus, dietary NAM supplementation in diabetic T1D mice prevented brain inflammation via NAD+-dependent deacetylation mechanisms, suggesting an increased action of sirtuin signaling.
Grants:	Instituto de Salud Carlos III PI21/00770 Ministerio de Economía y Competitividad PI21/00817 Instituto de Salud Carlos III PI21/00817
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Activated microglia ; Macrophage ; Neuroinflammation ; Neurological disease ; Neuropathy ; Sirtuin ; Type 1 diabetes mellitus
Published in:	Nutrients, Vol. 15 Núm. 14 (july 2023) , p. 3083, ISSN 2072-6643

DOI: 10.3390/nu15143083
PMID: 37513501

15 p, 4.7 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles