Protective Effects of 1-Methylnicotinamide on Aβ1-42-Induced Cognitive Deficits, Neuroinflammation and Apoptosis in Mice

The neurotoxicity of A beta peptides has been well documented, but effective neuroprotective approaches against A beta neurotoxicity are unavailable. In the present study, we investigated effects of 1-Methylnicotinamide (MNA), known as a main metabolite of nicotinamide (NA), on the impairment of learning and memory induced by A beta and the underlying mechanisms. We found that intragastric administration of MNA at 100 or 200 mg/kg for 3 weeks significantly reversed bilateral intrahippocampal injection of A beta(1-42)-induced cognitive impairments in the Morris water maze (MWM), Y-maze and Novel object recognition tests. Furthermore, MNA suppressed A beta(1-42)-induced neuroinflammation, characterized by suppressed activation of microglia, decreased the expression of IL-6, TNF-alpha and nuclear translocation of NF-kappa B p65, as well as attenuated neuronal apoptosis as indicated by decreased TUNEL-positive cells and ratio of caspase-3 fragment to procaspase-3, and increased ratio of Bcl-2/Bax in the hippocampus. Our results show that MNA may ameliorate A beta(1-42)-induced cognition deficits, which is involved in inhibition of neuroinflammation and apoptosis mediated by NF-kappa B signaling, suggesting that MNA could have potential therapeutic value for AD.