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mGlu5 receptors and cellular prion protein mediate amyloid-ß-facilitated synaptic long-term depression in vivo.
Hu, Neng-Wei; Nicoll, Andrew J; Zhang, Dainan; Mably, Alexandra J; O'Malley, Tiernan; Purro, Silvia A; Terry, Cassandra; Collinge, John; Walsh, Dominic M; Rowan, Michael J.
Afiliación
  • Hu NW; Department of Pharmacology and Therapeutics, and Trinity College Institute of Neuroscience, Biotechnology Building, Trinity College Dublin, Dublin 2, Ireland.
  • Nicoll AJ; Medical Research Council Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
  • Zhang D; Department of Pharmacology and Therapeutics, and Trinity College Institute of Neuroscience, Biotechnology Building, Trinity College Dublin, Dublin 2, Ireland.
  • Mably AJ; Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
  • O'Malley T; Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
  • Purro SA; Medical Research Council Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
  • Terry C; Medical Research Council Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
  • Collinge J; Medical Research Council Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
  • Walsh DM; Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
  • Rowan MJ; Department of Pharmacology and Therapeutics, and Trinity College Institute of Neuroscience, Biotechnology Building, Trinity College Dublin, Dublin 2, Ireland.
Nat Commun ; 5: 3374, 2014 Mar 04.
Article en En | MEDLINE | ID: mdl-24594908
NMDA-type glutamate receptors (NMDARs) are currently regarded as paramount in the potent and selective disruption of synaptic plasticity by Alzheimer's disease amyloid ß-protein (Aß). Non-NMDAR mechanisms remain relatively unexplored. Here we describe how Aß facilitates NMDAR-independent long-term depression of synaptic transmission in the hippocampus in vivo. Synthetic Aß and Aß in soluble extracts of Alzheimer's disease brain usurp endogenous acetylcholine muscarinic receptor-dependent long-term depression, to enable long-term depression that required metabotropic glutamate-5 receptors (mGlu5Rs). We also find that mGlu5Rs are essential for Aß-mediated inhibition of NMDAR-dependent long-term potentiation in vivo. Blocking Aß binding to cellular prion protein with antibodies prevents the facilitation of long-term depression. Our findings uncover an overarching role for Aß-PrP(C)-mGlu5R interplay in mediating both LTD facilitation and LTP inhibition, encompassing NMDAR-mediated processes that were previously considered primary.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Depresión Sináptica a Largo Plazo / Receptor del Glutamato Metabotropico 5 Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2014 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Depresión Sináptica a Largo Plazo / Receptor del Glutamato Metabotropico 5 Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2014 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Reino Unido