Tyrosine kinase signaling involved in glutamate-induced astrocyte proliferation

Proliferation of astrocytes is a common response of the CNS to injury and disease. The mechanisms controlling the proliferation of astrocytes are of great interest. In this paper, the signaling pathways underlying glutamate-induced astrocyte proliferation are investigated. Glutamate stimulates the proliferation of non-synchronized, subconfluent cultures of rat cortical astrocytes. Glutamate-induced cell proliferation is not prevented by inhibitors of G protein, protein kinase A, protein kinase C, phosphatidylinositol 3 kinase, extracellular signal-regulated kinase, or phospholipase A2. However, the tyrosine kinase inhibitors Genistein and Herbimycin A inhibit the glutamate-induced proliferation. Moreover, this proliferation is mediated by the activation of glutamate metabotropic receptors. These results suggest that glutamate induces astrocyte proliferation through a tyrosine kinase pathway.