English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/127137
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Blocking Effects of Human Tau on Squid Giant Synapse Transmission and Its Prevention by T-817 MA

AutorMoreno, Herman; Choi, Soonwook; Yu, Eunah; Brusco, Janaina; Ávila, Jesús ; Moreira, Jorge E.; Sugimori, Mutsuyuki; Llinás, Rodolfo R.
Palabras claveTauopathies
Synaptic Vesicles
Human tau
Neuro-protective agent
Synaptic transmission
Altzheimer’s disease
Fecha de publicaciónmay-2011
EditorFrontiers Media
CitaciónFrontiers in Synaptic Neuroscience 3: 3 (2011)
ResumenFilamentous tau inclusions are hallmarks of Alzheimer’s disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicity
Identificadoresissn: 1663-3563
Aparece en las colecciones: (CBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Avila Jesus Blocking effects.pdf892,62 kBAdobe PDFVista previa
Mostrar el registro completo

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.