Early age changes in mRNA expression related to NAD-dependent enzymes and mitochondrial proteins in the brain cortex of an Alzheimer’s disease mouse model

Abstract

Oxidative stress and disturbances of mitochondria function in the brain have been recognized to play a crucial role in the pathophysiological mechanism of Alzheimer’s Disease (AD). However, little is known about these changes at an early age of AD, which could be crucial for therapeutic strategy for the disease. In this study, we used biochemical, and quantitative polymerase chain reaction for determination of expression of genes encoding enzymes related to the antioxidative defence including Sirtuins (Sirts) and DNA-bound poly (ADP-ribose) polymerases (PARPs). Moreover, expression of genes related to mitochondrial dynamic, biogenesis and function in the brain cortex of 3- and 6-month-old FVB mice with London mutation (V7171) was analysed and compared with mice without transgene. Results indicated significant decreases in mRNA expression encoding SOD2, Sirt1 and PARP1 in the 3-month-old AD Tg mice and an increase in expression of PARP-1 in the 6-month-old AD Tg. Although levels of mRNA encoding subunits of mitochondrial respiratory complexes (I-III) were negligible altered, there was upregulation of gene encoding subunit of complex IV and proteins related to mitochondria biogenesis and dynamic, such as the Neuronal Respiratory Factors (NRF1) and NRF2, Opa1, Fis1, and Drp1 in the AD mice. Our data indicate downregulation of genes related to antioxidation and activation of genes encoding mitochondrial biogenesis and fission / fusion at early age of the AD mice. The ability to identify changes in gene expression for Sirt1, SOD2, Fis1 and Drp1 at an early age suggest potential therapeutic targets for retarding the pathological progression in AD.