Astroglial and microglial activation in the wistar rat ventral tegmental area after a single striatal injection of 6-hydroxydopamine

Abstract

Astroglial and microglial activation were analyzed in the ventral tegmental area (VTA) in adult male Wistar rats, after an unilateral striatal 6-hydroxydopamine (6-OHDA) injection. Different doses (8, 4, and 1 microg) of 6-OHDA were injected in the left side of the neostriatum; animals were sacrificed 22 days later. Control animals received an injection of the same volume of the solvent. The tyrosine hydroxylase (TH) positive dopamine cells, the glial fibrillary acidic protein (GFAP) immuno -labeled astrocytes, and the OX42 immunoreactive microglia were visualized by means of immunohistochemistry and quantified by stereologic methods employing the optical dissector and the point intercepts. The number and the density of TH immunoreactive cell bodies were decreased by 45% and 46%, respectively, in the sampled field of the ipsilateral VTA of 8 microg 6-OHDA injected rats. The GFAP immunohistochemistry revealed in the ipsilateral VTA increases the number and density of astroglial cells (154% and 166% of control, respectively) in the rats with a higher dose of the 6-OHDA, and also in the volume fraction of the astroglial processes after 8 microg (41% of control) and 4 microg (24% of control) of 6-OHDA. Increased number (76% of control) and density (77% of control) of OX42 microglial labeled profiles and microglial processes (51% of control) were found in the ipsilateral VTA of the 8 microg 6-OHDA injected animals. These results suggest that the retrograde degeneration of the mesostriatal dopamine pathways, induced by a striatal injection of 6-OHDA, leads to astroglial and microglial reactions in the VTA. The interaction between activated glial cells may be involved in the wounding and repair events in the partial lesioned system, and also in the trophic paracrine responses in the surviving VTA dopamine neurons.