Astroglial and microglial reaction after a partial nigrostriatal degeneration induced by the striatal injection of different doses of 6-hydroxydopamine.
Astroglial and microglial activation was analyzed in adult male Wistar rats after a unilateral striatal injection of different doses (8, 4 and 1 micrograms) of 6-hydroxydopamine (6-OHDA). Control animals received the injection of the same volume of the solvent. The rotational behavior was registered by a rotometer 24 and 72 hours, 7, 10, 14 and 22 days after lesion. Following, animals were sacrificed and the tyrosine hydroxylase (TH) positive dopamine cells, the glial fibrillary acidic protein (GFAP) immunolabeled astrocytes and the OX42 immunoreactive microglia were visualized by mean of immunohistochemistry and quantified by stereologic method employing the optical disector and the point intercepts. The apomorphine (0.5 mg/kg)-induced circling behavior was seen only after 8 micrograms of 6-OHDA from 72 hours postlesion until sacrifice. Decreases of the TH immunoreactive terminals and cell bodies were found in the sampled fields of the striatum and pars compacta of the substantia nigra (SNc), respectively, after 8 and 4 micrograms of 6-OHDA. The GFAP immunohistochemistry revealed increases in the number/density of astroglial cells in the ipsilateral neostriatum (137% of control) and ipsilateral SNc (83% of control) and also in the volumeal fraction of the astroglial processes in the ipsilateral neostriatum (30% of control) and ipsilateral SNc (38% of control) in the rats with higher dose of the neurotoxin. Increases in the number of OX42 microglial labeled profiles and in the volumeal fraction of microglial processes were found in the ipsilateral neostriatum (67% and 27%, respectively, of control) and ipsilateral SNc (100% and 50%, respectively, of control) in the 8 micrograms 6-OHDA injected rats. These results suggest that the retrograde degeneration induced by a intrastriatal injection of a small dose of the 6-OHDA leads to an astroglial and microglial reaction in the nigrostriatal dopamine pathway. The interaction between activated glial cells may be involved in the wounding and repair events in the partial lesioned nigrostriatal system as well as in the paracrine responses to surviving dopamine neurons.
Laboratory of Neuroregeneration, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 2415 05508-900-São Paulo, Brazil.,
Dose-Response Relationship, Drug
Glial Fibrillary Acidic Protein
Pub Type(s)Journal Article