Transient and Widespread Astroglial Activation in the Brain after a Striatal 6-Ohda-Induced Partial Lesion of the Nigrostriatal System

Abstract

The authors have previously described astroglial activation in the ipsilateral nigrostriatal system and ventral tegmental area following small doses of 6-hydroxydopamine (6-OHDA) injected unilaterally in the striatum. This article further evaluated astroglial reactivity in several brain regions after striatal 6-OHDA-induced punctate lesion in the nigrostriatal pathway. Adult male Wistar rats received a unilateral stereotaxical injection of the 6-OHDA (8 microg/4 microl) in the neostriatum and sacrificed 1 or 3 weeks later. Control animals received only solvent. Immunohistochemistry was employed for visualization of the tyrosine hydroxylase (TH), marker for dopamine cells, and glial fibrillary acidic protein (GFAP), marker for astrocytes. TH immunoreactive terminals disappeared in the striatum close to the injection site and a disappearance of a small number of a defined population of dopamine cell bodies was observed in the ipsilateral pars compacta of the substantia nigra (SNc). No dopamine lesion was detected in the contralateral nigrostriatal pathway. Astroglial reaction was seen close to the lesion in the neostriatum and in the ipsilateral SNc of the 1 week 6-OHDA lesioned rats. Specific stereological tools employing point intercepts and rotator, revealed an increased presence of reactive astrocytes in many forebrain regions like frontal, parietal and piriform cortex, septum, neostriatum and SNc, bilaterally, and also corpus callosum after 1 week of 6-OHDA injection. The astroglial activation was characterized by increases in the size of the cell body and/or processes. Astrocytic reaction was found only in the ipsilateral nigrostriatal pathway by 3 weeks of 6-OHDA, a slight activation also remaining in the ipsilateral septum and piriform cortex. Astrocytic reaction was seen in the solvent-injected rats only in the neostriatum close to the needle track. The transient widespread astroglial reaction observed in many brain regions following a striatal injection of 6-OHDA may represent a global paracrine trophic response in the brain.

Downregulation of glial glutamate transporters after dopamine denervation in the striatum of 6‐hydroxydopamine‐lesioned rats

“…These results are consistent with previous studies found in the 6-OHDA-lesioned model (Sheng et al, 1993;Chen et al, 2002;Rodrigues et al, 2004;Gomide et al, 2005) and in MPTP models (Chen et al, 2002) and it appears that the GFAP expression remained upregulated even after the main wave of neuronal death. This increase in GFAP staining is likely due to an increase in astrocyte numbers and sprouting of processes and end-feet, i.e., astrogliosis (Sheng et al, 1993;Gomide et al, 2005), and many of these astrocytes turn reactive (Chen et al, 2002(Chen et al, , 2004. The astrocytic reaction is presumed to result from stress that results from degeneration of dopaminergic terminals in the striatum and neurons (Sheng et al, 1993;Gomide et al, 2005).…”

“…This increase in GFAP staining is likely due to an increase in astrocyte numbers and sprouting of processes and end-feet, i.e., astrogliosis (Sheng et al, 1993;Gomide et al, 2005), and many of these astrocytes turn reactive (Chen et al, 2002(Chen et al, , 2004. The astrocytic reaction is presumed to result from stress that results from degeneration of dopaminergic terminals in the striatum and neurons (Sheng et al, 1993;Gomide et al, 2005). In the substantia nigra, the astrocytic reaction is likely due to the toxic effects of 6-OHDA and the degeneration of the dopaminergic neurons in the compacta.…”

Effect of 6-hydroxydopamine (6-OHDA) on proliferation of glial cells in the rat cortex and striatum: evidence for de-differentiation of resident astrocytes

“…A similar upregulation of GFAP has been shown in 6-OHDA-or MPTP-lesion models in which the neurotoxins are injected directly into the striatum (Chadi and Gomide 2004;Gomide et al 2005;Henning et al 2008;Yoo et al 2005), the median forebrain bundle (Henning et al 2008;Stromberg et al 1986), or the substantia nigra (Chung et al 2008;Sheng et al 1993). Similar to our findings, the activation of astrocytes in these studies is not restricted to the direct sites of 6-OHDA or MPTP injection but comprise various brain regions (Chadi and Gomide 2004;Gomide et al 2005) that represent target areas of dopaminergic projections. These observations suggest that the degeneration of the dopaminergic neurons themselves might result in reactive gliosis in the projection areas of their fibers.…”

S100ß and fibroblast growth factor-2 are present in cultured Schwann cells and may exert paracrine actions on the peripheral nerve injury

“…It seems possible that a trophic interaction of reactive satellite glia/Schwann cells and peripheral neurons is related to neuronal protection and/or nerve regeneration after axotomy 2 . It is likely that the satellite glia is also related to a continuous regulation of function and plasticity in peripheral sensory neurons as described for astrocytes in the lesioned central nervous system 20,[24][25][26] .…”