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Presynaptic Homeostasis Opposes Disease Progression in Mouse Models of ALS-Like Degeneration: Evidence for Homeostatic Neuroprotection.
Orr, Brian O; Hauswirth, Anna G; Celona, Barbara; Fetter, Richard D; Zunino, Giulia; Kvon, Evgeny Z; Zhu, Yiwen; Pennacchio, Len A; Black, Brian L; Davis, Graeme W.
Afiliación
  • Orr BO; Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94941, USA.
  • Hauswirth AG; Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94941, USA.
  • Celona B; Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
  • Fetter RD; Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94941, USA.
  • Zunino G; Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94941, USA.
  • Kvon EZ; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Zhu Y; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Pennacchio LA; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; U.S. Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA; Comparative Biochemistry Program, University of California, Berkeley, CA 94720, USA.
  • Black BL; Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
  • Davis GW; Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94941, USA. Electronic address: graeme.davis@UCSF.edu.
Neuron ; 107(1): 95-111.e6, 2020 07 08.
Article en En | MEDLINE | ID: mdl-32380032
Progressive synapse loss is an inevitable and insidious part of age-related neurodegenerative disease. Typically, synapse loss precedes symptoms of cognitive and motor decline. This suggests the existence of compensatory mechanisms that can temporarily counteract the effects of ongoing neurodegeneration. Here, we demonstrate that presynaptic homeostatic plasticity (PHP) is induced at degenerating neuromuscular junctions, mediated by an evolutionarily conserved activity of presynaptic ENaC channels in both Drosophila and mouse. To assess the consequence of eliminating PHP in a mouse model of ALS-like degeneration, we generated a motoneuron-specific deletion of Scnn1a, encoding the ENaC channel alpha subunit. We show that Scnn1a is essential for PHP without adversely affecting baseline neural function or lifespan. However, Scnn1a knockout in a degeneration-causing mutant background accelerated motoneuron loss and disease progression to twice the rate observed in littermate controls with intact PHP. We propose a model of neuroprotective homeostatic plasticity, extending organismal lifespan and health span.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terminales Presinápticos / Canales Epiteliales de Sodio / Neuroprotección / Homeostasis / Plasticidad Neuronal Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terminales Presinápticos / Canales Epiteliales de Sodio / Neuroprotección / Homeostasis / Plasticidad Neuronal Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos