1-Methylnicotinamide attenuates lipopolysaccharide-induced cognitive deficits via targeting neuroinflammation and neuronal apoptosis

• Published in: International immunopharmacology Vol. 77; p. 105918
• Main Authors: Mu, Rong-hao, Tan, Yuan-zhi, Fu, Li-li, Nazmul Islam, Mohammad, Hu, Mei, Hong, Hao, Tang, Su-su
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2019; Elsevier BV
• Subjects: 1-Methylnicotinamide; Alzheimer's disease; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Astrocytes; BAX protein; Bcl-2 protein; Caspase-3; Cell activation; Cognition; Cognition deficits; Cognition Disorders - chemically induced; Cognition Disorders - drug therapy; Cognition Disorders - immunology; Cognitive ability; Cortex (frontal); Cytokines; Frontal Lobe - drug effects; Hippocampus; Hippocampus - drug effects; Inflammation; Interleukin 6; Interleukin-6 - immunology; Lipopolysaccharide; Lipopolysaccharides; Male; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Memory Disorders - immunology; Metabolites; Mice, Inbred ICR; Microglia; Neurodegenerative diseases; Neuroinflammation; Neuronal apoptosis; Neurons - drug effects; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; NF-κB protein; Niacinamide - analogs & derivatives; Niacinamide - pharmacology; Niacinamide - therapeutic use; Nicotinamide; Object recognition; Pattern recognition; Transcription Factor RelA - immunology; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-α; Lipopolysaccharide; Cognition deficits; Neuroinflammation; Neuronal apoptosis; 1-Methylnicotinamide
• DOI: 10.1016/j.intimp.2019.105918
• ISSN: 1567-5769; 1878-1705

•1-Methylnicotinamide improves LPS-induced memory impairment in mice.•1-Methylnicotinamide inhibits LPS-induced neuroinflammatory response in the hippocampus and frontal cortex.•1-Methylnicotinamide inhibits LPS-induced glial cells activation in the hippocampus and frontal cortex.•1-Methylnicotinamide inhibits LPS-induced neuronal apoptosis in the hippocampus and frontal cortex. Alzheimer’s disease (AD) is a neurodegenerative disease that affects cognition and behavior. The neuroinflammatory response in the brain is an important pathological characteristic in AD. In this study, we investigated the neuroprotective effects of 1-Methylnicotinamide (MNA), known as the main metabolite of nicotinamide, on reducing lipopolysaccharide (LPS)-induced cognitive deficits via targeting neuroinflammation and neuronal apoptosis. We found that the mice treated with LPS exhibited cognitive deficits in the novel object recognition, Morris water maze and Y-maze avoidance tests. However, intragastric administration of MNA (100 or 200 mg/kg) for 3 weeks significantly attenuated LPS-induced cognitive deficits in mice. Importantly, MNA treatment suppressed the protein expression of nuclear factor-kappa B p65 (NF-κB p65), pro-inflammatory cytokines (TNF-α, IL-6) and decreased the activation of microglia and astrocytes in the hippocampus and frontal cortex of LPS-induced mice. In addition, MNA treatment suppressed neuronal apoptosis by reducing the number of TUNEL-positive cells, caspase-3 activation and increasing the level of Bcl-2/Bax ratio in the hippocampus and frontal cortex. These findings indicate that MNA could be a potential neuroprotective drug in neurodegenerative diseases such as AD.