AGE-RELATED EXPRESSION OF CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE II A IN THE HIPPOCAMPUS AND CEREBRAL CORTEX OF SENESCENCE ACCELERATED MOUSE PRONE/8 MICE IS MODULATED BY ANTI-ALZHEIMER'S DISEASE DRUGS

Senescence-accelerated mouse (SAM) prone/8 (SAMP8) is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits such as Alzheimer's disease (AD) at the gene and protein levels, and SAM resistant/1 (SAMR1) is its normal control. Calcium/calmodulin-dependent protein kinase 11-alpha (CaMKII alpha) is one of the most abundant subunits of calcium/calmodulin-dependent protein kinase 11 in cerebral cortex and hippocampus, and is closely linked to AD. In this study, we used real time fluorescence quantitative PCR (RT-PCR) and Western blot techniques to examine the expression of CaMKII alpha mRNA and protein in the cerebral cortex and hippocampus of SAMP8 both with aging and following treatment with anti-AD drugs (for example, natural product huperzine A (HupA) and traditional Chinese medicinal prescription Liu-Wei-Di-Huang decoction (LW), Ba-Wei-Di-Huang decoction (BW), Huang-Lian-Jie-Du decoction (HL), Dang-Gui-Shao-Yao-San (DSS) and Tiao-Xin-Fang decoction (TXF)). The results showed that the levels of both CaMKII alpha mRNA and protein decreased significantly in the cerebral cortex of SAMR1 with aging, but increased significantly in the cerebral cortex of SAMP8. Compared with age-matched SAMR1, the expression of mRNA and protein of CaMKII alpha significantly increased in the cerebral cortex and hippocampus of SAMP8 after 10 months of age. After SAMP8 was treated with the previously mentioned drugs, the abnormally high expression of CaMKII alpha was relatively down-regulated. These results indicated that the expression of CaMKII alpha in the brain of SAMP8 was abnormal and that this abnormality could be reversed with anti-AD drugs. These data suggest that CaMKII alpha may play an important role in the age-related cognitive deterioration in AD, and may be a potential targets for anti-AD drugs. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.