The rat with permanent occlusion of the bilateral common carotid arteries (2VO) is useful model for the study of dementia. The expression changes of amyloid precursor protein (APP), secretase, alpha7 nicotinic acetylcholine receptor (alpha7NicR) and acetylcholine esterase (AChE), which are involved in Alzheimer's disease, were examined by quantitative RT/PCR in this model rat brain. The expression of APP, alpha7NicR and secretase were increased 4 d after 2VO. The alpha7NicR level at 2 d after operation already tended to increase. These result suggest that alpha7NicR expression was enhanced at early stage of brain ischemia. Using this model to find drugs which regulate the alpha7NicR expression will be useful to assay the materials with anti-dementive effect.

ABSTRACT:The pathogenesis of Alzheimer' s disease (AD) is complicated and multifactorial, and is under the influence of genetic regulation. The NG108-15 cell line, a neuronal cell line, once differentiated exhibits neuron-like in morphology and intercellular synaptic junction formation. We, thus, hypothesize that the differentiation process may alter the expression patterns of AD-related genes in this cell line. This study primarily aimed to compare the expression patterns of five AD-related genes, namely AChE, COX-2, α7 nAChR, γ-secretase, and APP between undifferentiated and differentiated NG108-15 cells by RT-PCR techniques. The cyclic AMP analogue dibutyryl cAMP (Bt 2 cAMP) and 12-O-tetradecanoyl-phorbol 13-acetate (TPA) were used to induce neuronal differentiation. The differentiated NG108-15 cells exhibited neuron-like morphology and intercellular network formation. The level of AChE mRNA in differentiated cells was significantly greater than in undifferentiated cells at 2 and 3 day post-induction. Also, COX-2 mRNA expression in differentiated cells at day 1 post-induction was significantly greater than that in undifferentiated cells. In contrast, the expression of α7 nAChR mRNA was significantly down-regulated in differentiated cells at 1 and 3 days post-induction, and the expression level of γ-secretase mRNA was also significantly reduced in differentiated cells at 3 days post-induction. Interestingly, no significant difference of the expression of APP mRNA was detected. Our findings in this study indicate that the patterns of mRNA expression of AD related-genes in NG108-15 cells are changed after differentiation induction by Bt 2 cAMP and TPA.

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