Nicotinamide Reduces Amyloid Precursor Protein and Presenilin 1 in Brain Tissues of Amyloid Beta-Tail Vein Injected Mice

Abstract

The purpose of this study is to investigate whether nicotinic acid (NA) and nicotinamide (NAM) reduce the Alzheimer disease (AD)-related gene expression in brain tissues of amyloid beta (Aβ)-injected mice. Male Crj:CD1 (ICR) mice were divided into 6 treatment groups; 1) control, 2) Aβ control, 3) Aβ + NA 20 mg/kg/day (NA20), 4) Aβ + NA40, 5) Aβ + NAM 200 mg/kg/day (NAM200), and 6) Aβ + NAM400. After 1-week acclimation period, the mice orally received NA or NAM once a day for a total of 7 successive days. On day 7, biotinylated Aβ42 was injected into mouse tail vein. At 5 hours after the injection, blood and tissues were collected. Aβ42 injection was confirmed by Western blot analysis of Aβ42 protein in brain tissue. NAM400 pre-treatment significantly reduced the gene expression of amyloid precursor protein and presenilin 1 in brain tissues. And, NAM200 and NAM400 pre-treatments significantly increased sirtuin 1 expression in brain tissues, which is accompanied by the decreased brain expression of nuclear factor kappa B by 2 doses of NAM. Increased expression of AD-related genes was attenuated by the NAM treatment, which suggests that NAM supplementation may be a potential preventive strategy against AD-related deleterious changes.

Nicotinamide Improves Functional Recovery via Regulation of the RAGE/JNK/NF-κB Signaling Pathway after Brain Injury

“…Our results followed the notion that NAM inhibits p-JNK and p-NF-κB in the AD mouse model [50,51]. Furthermore, we also observed the increased immunoreactivity of Iba-1 and RAGE, in the ipsilateral side of the cortex and CA3 region of the hippocampus of the SWI mice group, compared to the saline-treated mice group.…”

“…Interestingly, NAM treatment inhibited these pathological markers in the ipsilateral cortex and hippocampus of injured mouse brains. Our results were consistent with previous results showing that NAM treatment increased the antioxidant enzymes and reduced the oxidative stress and amyloid precursor protein (Aβ generating protein) in Aβ injected mice [50]. Likewise, our immunohistological results revealed increased expression levels of active JNK in the cortical region of the injured mouse brains.…”

“…Logically, from these results, we can hypothesize that the reversal effects of NAM treatment might be attributable to the reduction in ligand-based activation of RAGE, and that NAM might interfere with the ligand-based interaction of RAGE in the injured mice brain. Previous studies have demonstrated that NAM treatment reduced the level of Aβ in the AD mouse model [50].…”

“…Previous reports have also demonstrated the protective effects of NAM treatment on neuroinflammation in the AD mouse model [52]. Recently, it was reported that NAM mononucleotide treatment inhibits neuroinflammation and neurodegeneration by inhibiting JNK in an AD animal model [50].…”

Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects

“…In addition to the identification of working mechanisms and major therapeutic targets, extensive efforts have also focused on suggesting nutritional strategies to prevent impairment of cognitive function induced by hyperglycemia. Among many suggested nutrients and functional food components, niacin, folate, vitamin B6, vitamin B12, resveratrol, and their analogues exert potentials to prevent or treat hyperglycemia, diabetes, MCI and AD [ 21 22 23 24 ].…”