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Secreted Amyloid Precursor Protein-Alpha Promotes Arc Protein Synthesis in Hippocampal Neurons.
Livingstone, Rhys W; Elder, Megan K; Barrett, Maya C; Westlake, Courteney M; Peppercorn, Katie; Tate, Warren P; Abraham, Wickliffe C; Williams, Joanna M.
Afiliación
  • Livingstone RW; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Elder MK; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Barrett MC; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Westlake CM; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Peppercorn K; Department of Biochemistry, Brain Health Research Centre, Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Tate WP; Department of Biochemistry, Brain Health Research Centre, Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Abraham WC; Department of Psychology, Brain Health Research Centre, Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
  • Williams JM; Department of Anatomy, Brain Health Research Centre, Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
Front Mol Neurosci ; 12: 198, 2019.
Article en En | MEDLINE | ID: mdl-31474829
Secreted amyloid precursor protein-α (sAPPα) is a neuroprotective and memory-enhancing molecule, however, the mechanisms through which sAPPα promotes these effects are not well understood. Recently, we have shown that sAPPα enhances cell-surface expression of glutamate receptors. Activity-related cytoskeletal-associated protein Arc (Arg3.1) is an immediate early gene capable of modulating long-term potentiation, long-term depression and homeostatic plasticity through regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor localization. Accordingly, we hypothesized that sAPPα may enhance synaptic plasticity, in part, by the de novo synthesis of Arc. Using primary cortical and hippocampal neuronal cultures we found that sAPPα (1 nM, 2 h) enhances levels of Arc mRNA and protein. Arc protein levels were increased in both the neuronal somata and dendrites in a Ca2+/calmodulin-dependent protein kinase II-dependent manner. Additionally, dendritic Arc expression was dependent upon activation of mitogen-activated protein kinase and protein kinase G. The enhancement of dendritic Arc protein was significantly reduced by antagonism of N-methyl-D-aspartate (NMDA) and nicotinic acetylcholine (α7nACh) receptors, and fully eliminated by dual application of these antagonists. This effect was further corroborated in area CA1 of acute hippocampal slices. These data suggest sAPPα-regulated plasticity within hippocampal neurons is mediated by cooperation of NMDA and α7nACh receptors to engage a cascade of signal transduction molecules to enhance the transcription and translation of Arc.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Mol Neurosci Año: 2019 Tipo del documento: Article País de afiliación: Nueva Zelanda Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Mol Neurosci Año: 2019 Tipo del documento: Article País de afiliación: Nueva Zelanda Pais de publicación: Suiza