Effects of nicotinamide treatment on mRNA expression of various enzymes involved in nad+ metabolism in Aβ(1-42) induced neurodegeneration

The aim of the present study is to research that the effects of nicotinamide treatment on mRNA expression of various enzymes (sirtuins, PARP-2, CD38) involved in NAD+ metabolism in Aβ(1-42) induced neurodegeneration. Impairment of energy metabolism in the development of Alzheimer's disease plays a central role. Changes in the activity of cytoplasmic and mitochondrial enzymes involved in glucose metabolism determines the course of the disease and its severity. NAD+, a coenzyme of metabolic reactions in cells, is required for cell survival, healthy aging and sirtuin activity. PARP-2 and CD38 enzymes exhibit requirements to NAD+ for their activity. PARP-2 plays central role in cell death pathways and DNA repair mechanisms. CD38 is involved in the regulation of Ca2+ levels. NAD+ dependent enzymes and enzymes involved in NAD+ synthesis are important therapeutic targets in obesity, diabetes, cancer and neurodegenerative diseases. In our study, Sprague-Dawley rats were used and divided into three groups as control (n=4), Aβ(1-42) (n=4) and Aβ(1-42) + 100 mg/kg NA (n=4). At the seventh day of treatment animals were decapited and brains were dissected on ice. Brain tissue samples were stored in -80˚C until the day of the experiment. Hippocampal tissues were used for experiments. The expression profile of SIRT1, SIRT2, PARP-2 and CD38 genes was determined by Real-Time PCR. Our results indicate that Aβ(1-42) treatment significantly down-regulated the expression of SIRT1 and did not cause any change in SIRT2, PARP-2, CD38 expressions in hippocampus when compared to control group. The nicotinamide treatment against Aβ significantly increased SIRT1 mRNA levels expression which were lowered by Aβ. This increase can be related with the elevated levels of NAD+ which can be caused by nicotinamide. Nicotinamide has neuroprotective effects through the regulation of gene expression, cognitive and cellular functions, and reduced plaque formation in Alzheimer disease models. The nicotinamide treatment against Aβ, led to a little increase to the expression of CD38 gene compared to the control group. It can effect the cell by regulating calcium channels, second messenger activities and cellular functions. According to the results we obtained from SIRT2 and PARP-2 expressions in the hippocampus, there were no significant differences between the experimental groups. In this study nicotinamide treatment against Aβ, caused upregulation of SIRT1 and CD38 enzymes involved in NAD+ metabolism in the neurodegeneration model induced by Aβ(1-42). The regulatory effect of nicotinamide on the expressions of SIRT1 and CD38 can be helpful for its neuroprotective role in Alzheimer disease and other neurodegenerative diseases.