Abstract
Alzheimer's disease (AD) is the most predominant age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregates of amyloid beta Aβ1-42 and tau hyperphosphorylation in the brain. It is considered to be the primary cause of cognitive dysfunction. The aggregation of Aβ1-42 leads to neuronal inflammation and apoptosis. Since vitamins are basic dietary nutrients that organisms need for their growth, survival, and other metabolic functions, in this study, the underlying neuroprotective mechanism of nicotinamide (NAM) Vitamin B3 against Aβ1-42 -induced neurotoxicity was investigated in mouse brains. Intracerebroventricular (i.c.v.) Aβ1-42 injection elicited neuronal dysfunctions that led to memory impairment and neurodegeneration in mouse brains. After 24 h after Aβ1-42 injection, the mice were treated with NAM (250 mg/kg intraperitoneally) for 1 week. For biochemical and Western blot studies, the mice were directly sacrificed, while for confocal and "immunohistochemical staining", mice were perfused transcardially with 4% paraformaldehyde. Our biochemical, immunofluorescence, and immunohistochemical results showed that NAM can ameliorate neuronal inflammation and apoptosis by reducing oxidative stress through lowering malondialdehyde and 2,7-dichlorofluorescein levels in an Aβ1-42-injected mouse brains, where the regulation of p-JNK further regulated inflammatory marker proteins (TNF-α, IL-1β, transcription factor NF-kB) and apoptotic marker proteins (Bax, caspase 3, PARP1). Furthermore, NAM + Aβ treatment for 1 week increased the amount of survival neurons and reduced neuronal cell death in Nissl staining. We also analyzed memory dysfunction via behavioral studies and the analysis showed that NAM could prevent Aβ1-42 -induced memory deficits. Collectively, the results of this study suggest that NAM may be a potential preventive and therapeutic candidate for Aβ1-42 -induced reactive oxygen species (ROS)-mediated neuroinflammation, neurodegeneration, and neurotoxicity in an adult mouse model.
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