REGULATION OF THROMBOSPONDIN IN THE REGENERATING MOUSE FACIAL MOTOR NUCLEUS

Thrombospondin (TSP) is a multifunctional extracellular matrix protein that plays a role in neuronal migration and axonal outgrowth in the d eveloping central nervous system. In the current study we have examine d the localization and regulation of TSP immunoreactivity (TSP-IR) dur ing neuronal regeneration in the axotomized facial motor nucleus using Western blotting and light and electron microscopy. Transection of th e facial nerve led to a gradual increase in TSP-IR in the regenerating motoneurons, peaking 4-7 days after injury (DAI). In addition to rege nerating neurons, axotomy also caused a rapid upregulation of TSP-IR o n activated microglia throughout the facial nucleus, with a maximum of 2-3 DAI, and a second increase at 14-21 DAI on microglial aggregates surrounding degenerating motoneurons and in neuronophagic microglia. I n summary, injury leads to the induction of thrombospondin on axotomiz ed neurons and activated microglia, peaking at the times of maximal po sttraumatic microglial proliferation and during neuronal phagocytosis. Since thrombospondin is a multimodal extracellular matrix protein wit h a variety of cell attachment sites, thrombospondin might serve to li nk microglia and injured neurons, followed by microglial proliferation and removal of the neuronal debris. (C) 1996 Wiley-Liss, Inc.