The investigation of acid sensing ion channels (ASICs) expression in a model of sporadic dementia of alzheimer's type in mice

The Investigation of Acid Sensing Ion Channels (ASICs) Expression in a Model of Sporadic Dementia of Alzheimer's Type in Mice Alzheimer's disease (AD) is a progressive neurodegenerative disease occuring with the neuron and synapse loss. It is stated that etiopathogenesis of the disease play the important roles of especially sodium permeable ion channels in neurons. Acid Sensitive Ion Channels (ASICs) are member of the amiloride-sensitive degenerin/epithelial Na + channel (DEG / ENAC) gene family. Common properties of ASICs are sensitive to pH changes. ASIC 1a, 2a, 2b and 4 are especially expressed in the brain. In this study, we aimed to determine expression of ASICs in brain tissues in the amiloid beta induced mice Alzheimer model. Balb C strain mice were used for the study. Mice were separated into 4 groups: Beta-amyloid group (n = 10), sham group (n = 10), treatment group (Beta-amyloid + amiloride group, n=10) and control group (n= 8). For the determination of ASIC1, 2, 3 and 4 expression were performed the immunohistochemistry, western blot and Real-time Polymerase Chain Reaction (RT- PCR) methods. For the detection of beta-amyloid-induced apoptosis were used Tunel method. According to results of RT-PCR analysis when compared with control group, it is detected that decrease in ASIC 1, 2 and 3 expression of other group didn't significant as statistical. According to result of Western Blot analysis while in terms of ASIC 1 and ASIC 2 wasn't observed significant differance among groups as statistical, it was detected a significant increase in Beta amyloid and Beta amyloid + Amilorid groups. The result of immunohistochemical stain showed that although there was no significant differance as statistical ( p>0.05) between groups in terms of ASIC1 and ASIC2, it was determined a significant increase of ASIC4 in Beta amyloid group compared with control Although there wasn't difference in terms of expression of ASIC1 in groups, it is showed that ASIC1 could be active at pH= 6.6 in AD. As a result, it is thought that ASICs may play a key role in AD ethiopathogenesis by increasing level of intracellular sodium ion through the increase expression of ASIC4 and the activation of ASIC1. Key Word: Alzheimer's Disease, Acid Sensing Ion Channels, Beta-amyloid Peptide(1-42)