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.

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.…”

Oxidative Stress in Parkinson's Disease; Parallels Between Current Animal Models, Human Studies and Cells

“…A progressive loss of dopaminergic neurons in the substantia nigra and loss of striatal innervation was shown. The low dose of rotenone mediated dopaminergic cell death by oxidative stress as previously demonstrated (Rodrigues, Gomide and Chadi 2004). An increase in astrocytes and microglia occurs in human PD, where they have been ascribed both a neuroprotective and deleterious role (Imamura et al 2003, Ishida et al 2006, Vila et al 2001).…”

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

“…A follow up study showed that GDNF transgene expression could be observed for up to six months and showed that GDNF levels were higher in the 6-OHDA model than in the healthy brain [210]. Since the 6-OHDA causes a large upregulation of astrocytes in the rat 6-OHDA model [211] it is likely that this increased GDNF level is due to the transfection of astrocytes, being greater in number in the 6-OHDA model than the healthy brain [210]. A previous study has shown that primary astrocytes extracted from the midbrain of the newborn rat are far less amenable to non-viral transfection than immortalized Neu7 astrocytes [96].…”