Temporal and spatial increase of astroglial basic fibroblast growth factor synthesis after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons

Abstract

The present study investigates the temporal and spatial changes of the cellular expression of basic fibroblast growth factor messenger RNA and immunoreactivity after a 6-hydroxydopamine-induced lesion in the nigrostriatal dopamine system. In situ hybridization revealed a sustained (from 4 h to two weeks) and strong (300–400% of control, at the peak intervals) increase of basic fibroblast growth factor messenger RNA in the pars compacta of the substantia nigra and the ventral tegmental area ipsilateral to the lesion. A short-lasting increase of basic fibroblast growth factor messenger RNA was observed in the ipsilateral pars reticulata of the substantia nigra (from 4–24 h, 300% of control) and neostriatum (24 h, 180% of control) as well as in the ipsilateral and contralateral hippocampus and neocortex (by 4 h, 200% of control). Brightfield microscopy showed an increased number of putative glial cells expressing the basic fibroblast growth factor messenger RNA signal. Basic fibroblast growth factor immunohistochemistry revealed on control brains the protein in the nuclei of glial cells throughout the forebrain and the midbrain and in the nuclei of neurons of the layer II of the retrosplenial granular cortex, the CA2 region of the hippocampus and the fasciola cinereum as well as in the nuclei of ependymal cells. The injection of 6-hydroxydopamine increased basic fibroblast growth factor immunoreactivity in the nuclei of astrocytes only within the ipsilateral substantia nigra and ventral tegmental area. By 2 h after the drug injection, the density of glial basic fibroblast growth factor-immunoreactive profiles was increased in the pars compacta of the substantia nigra and the ventral tegmental area. The density, size and intensity of the astroglial basic fibroblast growth factor immunoreactive nuclei were increased in the entire substantia nigra and the ventral tegmental area at 72 h, and peaked one week after the 6-hydroxydopamine injection. The saline injection promoted a time-dependent increase in the density of the glial basic fibroblast growth factor immunoreactivity but only in the ipsilateral pars compacta of the substantia nigra. In conclusion, the dopamine cell degeneration may give rise to extracellular signals activating the surrounding astroglia, leading to a sustained increased synthesis of astroglial basic fibroblast growth factor, which may exert neuroprotective action and increase repair on the nigrostriatal dopamine system.