P2X receptor overexpression induced by soluble oligomers of amyloid beta peptide potentiates synaptic failure and neuronal dyshomeostasis in cellular models of Alzheimer's disease

Neuropharmacology
F Sáez-OrellanaJ Fuentealba

Abstract

The most common cause of dementia is Alzheimer's disease. The etiology of the disease is unknown, although considerable evidence suggests a critical role for the soluble oligomers of amyloid beta peptide (Aβ). Because Aβ increases the expression of purinergic receptors (P2XRs) in vitro and in vivo, we studied the functional correlation between long-term exposure to Aβ and the ability of P2XRs to modulate network synaptic tone. We used electrophysiological recordings and Ca2+ microfluorimetry to assess the effects of chronic exposure (24 h) to Aβ oligomers (0.5 μM) together with known inhibitors of P2XRs, such as PPADS and apyrase on synaptic function. Changes in the expression of P2XR were quantified using RT-qPCR. We observed changes in the expression of P2X1R, P2X7R and an increase in P2X2R; and also in protein levels in PC12 cells (143%) and hippocampal neurons (120%) with Aβ. In parallel, the reduction on the frequency and amplitude of mEPSCs (72% and 35%, respectively) were prevented by P2XR inhibition using a low PPADS concentration. Additionally, the current amplitude and intracellular Ca2+ signals evoked by extracellular ATP were increased (70% and 75%, respectively), suggesting an over activation of purinergic neurotra...Continue Reading

Citations

Mar 23, 2018·Journal of Lipid Research·Jianjia FanCheryl L Wellington
Jul 18, 2020·Medicinal Research Reviews·Francesco CalzaferriAntonio G García
Dec 4, 2019·Frontiers in Pharmacology·Pamela Andrea GodoyJorge Fuentealba
Jun 26, 2020·Frontiers in Molecular Neuroscience·Linda FrancistiováMiguel Díaz-Hernández
Sep 18, 2020·Neuroscience·Rashmi Das, Subashchandrabose Chinnathambi
Jul 12, 2020·The Journal of Steroid Biochemistry and Molecular Biology·Sonja SivcevHana Zemkova
Jun 3, 2021·Cells·Stefania MerighiDavide Ferrari
Jul 17, 2021·Neural Regeneration Research·Jessica D PanesJorge Fuentealba
Aug 4, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Pamela A GodoyJorge Fuentealba
Aug 28, 2020·Brain Research Bulletin·Li Zhang, Handong Wang

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