Amyloid-β(25-35) Modulates the Expression of GirK and KCNQ Channel Genes in the Hippocampus

• DOI: 10.1371/journal.pone.0134385
• Publication Date: 2015-07-28T17:56:52Z
• Authors: Jennifer Mayordom...; Javier Yajeya; Juan D. Navarro-L...; Lydia Jiménez-Díaz
• Keywords: 0301 basic medicine; Amyloid beta-Peptides; KCNQ Potassium Channels; Reverse Transcriptase Polymerase Chain Reaction; Science; Q; R; Real-Time Polymerase Chain Reaction; Hippocampus; Peptide Fragments; Rats; 3. Good health; 03 medical and health sciences; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Gene Expression Regulation; Medicine; Animals; RNA, Messenger; Rats, Wistar; Research Article

During early stages of Alzheimer's disease (AD), synaptic dysfunction induced by toxic amyloid-β (Aβ) is present before the accumulation histopathological hallmarks disease. This scenario produces impaired functioning neuronal networks, altered patterns synchronous activity and severe functional deficits mainly due to hyperexcitability hippocampal networks. The molecular mechanisms underlying these alterations remain unclear but evidence, shown our laboratory others, points involvement receptors/channels which modulate excitability, playing a pivotal role in Aβ-induced AD pathogenesis. In particular, two potassium channels that control G protein-coupled activated inwardly-rectifying channel (GirK), voltage-gated K (KCNQ), have been recently linked Aβ pathophysiology hippocampus. Specifically, using Aβ25-35, we previously found GirK conductance greatly decreased hippocampus, similar effects also reported on KCNQ conductance. Thus, study, goal was determine effect transcriptional expression pattern 17 genes encoding neurotransmitter receptors associated maintain excitatory-inhibitory neurotransmission balance circuits, with special focus channels. For this purpose, designed systematic reliable procedure analyze mRNA reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) rat slices incubated Aβ25-35. We that: 1) down-regulated ionotropic GluN1 metabotropic mGlu1 glutamate receptor subunits as other models; 2) reduced gene levels GirK2, 3, 4 subunits, KCNQ2 3 did not change its GABAB M1 receptors, respectively. Our results provide evidence can could affect learning memory processes AD.