Astroglial and Microglial Reaction After A Partial Nigrostriatal Degeneration Induced by The Striatal Injection of Different Doses of 6-Hydroxydopamine

Abstract

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.

Cellular pathology of Parkinson?s disease: astrocytes, microglia and inflammation

“…The finding of an astrocytic response due to 6-OHDA was confirmed by others (Gordon et al 1997;Pasinetti et al 1999;Rodrigues et al 2001), whereas (Depino et al 2003) claimed that an astrocytic reaction did not occur following 6-OHDA injections.…”

Cellular iron status influences the functional relationship between microglia and oligodendrocytes

“…GFAP was used to identify astrocytes and OX-42 to identify microglia (McRae et al, 1996;Rodrigues et al, 2001). Based on the expression of MBP, we have obtained separate cultures enriched for either mature oligodendrocytes or microglia that reached more than 90 or 95% purity respectively.…”

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

“…Other series of sections was submitted to immunohistochemistry of glial fi brillary acid protein (GFAP), as a marker for astrocytes. Immunoreactivity was detected by the avidin-biotin peroxidase technique [23][24][25] . Sections were washed for 2x10 min in PBS, and incubated with 5% normal goat serum for 30 min at room temperature.…”