Astrocytes respond to central nervous system (CNS) injury in ways that are both supportive and inhibitory of neuronal survival-and regeneration. Previous studies of the astrocytic response to injury and disease have focused primarily on morphological changes; including proliferation, process extension, and increased levels of the glial intermediate filament protein, GFAP. These gliotic responses are thought to be detrimental to regeneration, however some astrocytes have been shown to engage in processes which appear to promote regeneration. These include phagocytosis of neuronal debris, and synthesis of both extracellular matrix proteins and numerous neurotrophic factors. A useful approach to identifying astrocytes engaged in growth promoting processes is to study the molecular processes involved in astrocyte function with the expectation that different molecular cascades may be initiated in growth- promoting vs. growth-inhibiting astrocytes. Accumulating evidence suggests that the balance between protein phosphorylation and dephosphorylation modulates many cellular functions, and protein tyrosine phosphorylation has been implicated in both astrocyte proliferation and differentiation. The phosphorylation state of proteins on tyrosine residues is regulated by the balance between protein tyrosine kinases (PTKs) which phosphorylate tyrosine residues and protein tyrosine phosphatases (PTPs) which dephosphorylate tyrosine residues. We have found a subset of astrocytes in the chick auditory brainstem that are immunopositive for the tyrosine phosphatase PTP1C. Following cochlea removal, there is a marked increase within the auditory brainstem nucleus, n. Magnocellularis (NM) both in the number of PTP1C positive astrocytes and in the length of their immunopositive fibers. This increase does not appear to be localized to GFAP-containing astrocytes and is not correlated with glial proliferation. The proposed experiments are designed to determine whether these PTP1C-positive astrocytes are involved in processes which are supportive of neuron survival following deafferentation and to elucidate the extracellular signals that increase PTP1C-immunoreactivity in these astrocytes. It is hoped that a more complete understanding of the molecular processes involved in astrocyte activation will provide insight into the growth- promoting and growth-inhibiting functions of astrocytes. This, in turn, may allow the development of clinically relevant strategies for improving neuronal survival and regeneration following injury.
