title: Dopamine agonists rescue Aβ-induced LTP impairment by Src-family tyrosine kinases.
abstract: Soluble forms of oligomeric amyloid beta (AβO) are involved in the loss of synaptic plasticity and memory, especially in early phases of Alzheimer's disease. Stimulation of dopamine D1/D5 receptors (D1R/D5R) is known to increase surface expression of synaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate subtype glutamate and N-methyl-D-aspartate subtype glutamate receptors and facilitates the induction of the late phase of long-term potentiation (LTP), probably via a related mechanism. In this study, we show that the D1/D5R agonist SKF38393 protects LTP of hippocampal CA1 synapses from the deleterious action of oligomeric amyloid beta. Unexpectedly, the D1R/D5R-mediated recovery of LTP is independent of protein kinase A or phospholipase C pathways. Instead, we found that the inhibition of Src-family tyrosine kinases completely abolished the protective effects of D1R/D5R stimulation in a cellular model of learning and memory.
authors.affiliation: Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors.forename: PingAn
authors.initials: P
authors.lastname: Yuan Xiang
authors.affiliation: RG Neuropharmacology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Janc
authors.affiliation: Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Grochowska
authors.affiliation: Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany; Leibniz Group 'Dendritic Organelles and Synaptic Function', Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Neurodegenerative Diseases, Magdeburg, Germany. Electronic address: kreutz@lin-magdeburg.de.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kreutz
authors.affiliation: RG Neuropharmacology, Leibniz Institute for Neurobiology, Magdeburg, Germany; German Center for Neurodegenerative Diseases, Magdeburg, Germany. Electronic address: reymann@lin-magdeburg.de.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Reymann
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D056547:CA1 Region, Hippocampal; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000502:physiology; D050641:Receptors, Dopamine D5 / Q000502:physiology; D012995:Solubility; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D019061:src-Family Kinases
keywords: Alzheimer disease; Amyloid beta oligomers (AβO); D1/D5 dopamine receptors; LTP; Src kinases