title: Differential control of thrombospondin over synaptic glycine and AMPA receptors in spinal cord neurons.
abstract: Thrombospondin-1 (TSP-1) is a large extracellular matrix protein secreted by astrocytes during development and inflammation. In the developing CNS, TSP-1 is involved in neuronal migration and adhesion, neurite outgrowth, and synaptogenesis. We investigated the effects of TSP-1 on neurons with mature synapses using immunocytochemistry, single-particle tracking, surface biotinylation, and calcium imaging. We show that in cultured rat spinal cord neurons TSP-1 decreased neuronal excitability by reducing the accumulation of excitatory AMPA receptors (AMPARs) and increasing that of inhibitory glycine receptors (GlyRs) in synapses. The effects of TSP-1 on GlyRs were dependent on the activation of excitatory receptors. These changes were abolished by blocking β1-integrins and mimicked by blocking β3-integrins. In the presence of TSP-1, AMPARs were less stabilized at synapses, increasing their lateral diffusion and endocytosis. Interestingly, TSP-1 counteracted the increased neuronal excitability and neuronal death induced by TNFα. These results suggest a role of TSP-1 in controlling the balance between excitation and inhibition which could help the recovery of normal synaptic activity after injury responses.
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, Paris, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Hennekinne
authors.forename: Sabrina
authors.initials: S
authors.lastname: Colasse
authors.forename: Antoine
authors.initials: A
authors.lastname: Triller
authors.forename: Marianne
authors.initials: M
authors.lastname: Renner
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018009:Receptors, Glycine / Q000819:agonists / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D018009:Receptors, Glycine; D019700:Thrombospondin 1; C582391:Thbs1 protein, rat