Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression

Giulia E. Tyzack, Sergey Sitnikov, Daniel Barson, Kerala L. Adams-Carr, Nike K. Lau, Jessica C. Kwok, Chao Zhao, Robin J. M. Franklin, Ragnhildur T. Karadottir, James W. Fawcett and András Lakatos ()
Additional contact information
Giulia E. Tyzack: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
Sergey Sitnikov: University of Cambridge
Daniel Barson: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
Kerala L. Adams-Carr: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
Nike K. Lau: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
Jessica C. Kwok: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
Chao Zhao: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
Robin J. M. Franklin: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
Ragnhildur T. Karadottir: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
James W. Fawcett: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK
András Lakatos: John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 0PY, UK

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: Abstract The role of remote astrocyte (AC) reaction to central or peripheral axonal insult is not clearly understood. Here we use a transgenic approach to compare the direct influence of normal with diminished AC reactivity on neuronal integrity and synapse recovery following extracranial facial nerve transection in mice. Our model allows straightforward interpretations of AC–neuron signalling by reducing confounding effects imposed by inflammatory cells. We show direct evidence that perineuronal reactive ACs play a major role in maintaining neuronal circuitry following distant axotomy. We reveal a novel function of astrocytic signal transducer and activator of transcription-3 (STAT3). STAT3 regulates perineuronal astrocytic process formation and re-expression of a synaptogenic molecule, thrombospondin-1 (TSP-1), apart from supporting neuronal integrity. We demonstrate that, through this new pathway, TSP-1 is responsible for the remote AC-mediated recovery of excitatory synapses onto axotomized motor neurons in adult mice. These data provide new targets for neuroprotective therapies via optimizing AC-driven plasticity.

Date: 2014
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DOI: 10.1038/ncomms5294

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