PTP1C INCREASES IN THE DEAFFERENTED AUDITORY BRAINSTEM

星形胶质细胞对中枢神经系统（CNS）损伤的反应方式， 既支持又抑制神经元的存活和再生。 先前关于星形胶质细胞对损伤和疾病的反应的研究 主要关注形态学变化;包括增殖， 突起延伸和胶质中间体水平增加 纤维蛋白原。这些神经胶质反应被认为是 对再生有害，然而一些星形胶质细胞已经被证明 参与似乎能促进再生的过程。这些包括 吞噬神经元碎片，并合成细胞外 基质蛋白和许多神经营养因子。的有用方法 鉴定参与生长促进过程的星形胶质细胞是为了研究 参与星形胶质细胞功能的分子过程 期望不同的分子级联可能在生长中启动- 促进与抑制生长的星形胶质细胞。 越来越多的证据表明，蛋白质和蛋白质之间的平衡 磷酸化和去磷酸化调节许多细胞功能， 而蛋白质酪氨酸磷酸化与这两个过程都有关系， 星形胶质细胞增殖和分化。的磷酸化状态 酪氨酸残基上的蛋白质的量受以下平衡的调节： 磷酸化酪氨酸残基的蛋白酪氨酸激酶（PTK）， 使酪氨酸脱磷酸化的蛋白酪氨酸磷酸酶（PTP 残基我们在鸡的听觉系统中发现了一个星形胶质细胞亚群， 酪氨酸磷酸酶PTP 1C免疫阳性的脑干。 耳蜗摘除后，听觉神经元内的 脑干核，n.大细胞（NM），PTP 1C的数量 阳性星形胶质细胞和其免疫阳性纤维的长度。 这种增加似乎并不局限于含有GFAP的细胞。 星形胶质细胞，与胶质细胞增殖无关。拟议 实验旨在确定这些PTP 1C阳性 星形胶质细胞参与支持神经元的过程， 存活后传入和阐明细胞外 信号增加这些星形胶质细胞中的PTP 1C免疫反应性。是 希望能更全面地了解 参与星形胶质细胞激活的研究将提供对 促进和抑制星形胶质细胞的生长功能。这反过来又 可能允许临床相关策略的发展， 损伤后的神经元存活和再生。

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.