Alterations in striatal glial fibrillary acidic protein expression in response to 6-hydroxydopamine-induced denervation

Abstract

Following injection of 6-hydroxydopamine (6-OHDA) into one side of the substantia nigra, immunohistochemical studies showed that the number of glial fibrillary acidic protein-positive [GFAP(+)] astrocytes in the striatum was significantly increased 1 day later and reached a maximum value, with intense immunoreactivity, 4 days after 6-OHDA injection. The number of GFAP(+) cells then gradually declined but was still 1.7 times the control value by 28 days postlesion. GFAP content, determined by immunoblot, and GFAP messenger RNA (mRNA) both reached maximal increases in the striatum 7 days after lesion: the mRNA returned to control values by 28 days, whereas GFAP content remained significantly elevated. Although the increases were all larger on the lesioned side, there were also significant changes on the contralateral side, as well as following saline injection. These results support the hypothesis that products released from damaged neurons are responsible for the induction of reactive gliosis, but cannot distinguish between effects mediated directly on the astrocytes or indirectly via other cells such as the microglia.