Extracellular matrix molecules play an important role in the formation of neuronal connections both during development and following injury. However, the molecular mechanisms by which extracellular matrix proteins participate in the reestablishment of functional synaptic connections following injury is unknown. Upregulation of inhibitory extracellular matrix proteins in neurodegenerative diseases, such as Huntington's disease, suggest that they may be associated with an altered molecular environment that results in neuronal death. This proposal addresses the general hypotheses: 1) that the induction of a persistent reactive state in astrocytes may differentially affect the induction of transgenic mice in which expression of extracellular matrix proteins, and 2) that the production of transgenic mice in which expression of extracellular matrix proteins by astrocytes is enhanced will alter reactive sprouting. By altering the spatial and temporal expression of the growth-inhibitory molecule, tenascin, processes that interfere with repair may be enhanced, resulting in disruption of cellular and molecular events involved in recovery. These proposed studies will examine whether extracellular matrix proteins are involved in reactive sprouting following a deafferentation lesion and the effects of elevated levels of tenascin on remodeling of glutamatergic acid.
