The astrocytic response to the dopaminergic denervation of the striatum

Abstract

Increasing evidence suggests that the dopaminergic degeneration which characterizes Parkinson's disease starts in the striatal dopamine terminals and progresses retrogradely to the body of dopamine cells in the substantia nigra. The role of striatal astrocytes in the striatal initiation of the dopaminergic degeneration is little known. This work was aimed at studying the astrocytic response to the dopaminergic denervation of the striatum. The injection of 6-hydroxydopamine (25 μg) in the lateral ventricle of adult Sprague-Dawley rats induced a fast (4 h) and selective (unaccompanied by unspecific lesions of striatal tissue or microgliosis) degeneration of the dopaminergic innervation of the striatum which was followed by a selective astrocytosis unaccompanied by microgliosis. This astrocytosis was severe and had a specific profile which included some (e.g. up-regulation of glial fibrillary acidic protein, GS, S100β, NDRG2, vimentin) but not all (e.g. astrocytic proliferation or differentiation from NG2 cells, astrocytic scars, microgliosis) the characteristics observed after the non-selective lesion of the striatum. This astrocytosis is similar to those observed in the parkinsonian striatum and, because it is was unaccompanied by changes in other striatal cells (e.g. by microgliosis), it may be suitable to study the role of striatal astrocytes during the dopaminergic denervation which characterizes the first stages of Parkinson's disease. The dopaminergic denervation of the striatum induced a severe astrogliosis with a specific profile which included some (e.g. up-regulation of GFAP, GS, S100β, NDRG2, vimentin) but not all (e.g. astrocytic proliferation or differentiation from NG2 cells, astrocytic scars, microgliosis) the characteristics observed after the non-selective striatal lesions. This response may help to understand the role of striatal astrocytes during the dopaminergic denervation which characterizes the first stages of PD. Cover Image for this issue: doi: 10.1111/jnc.13336.

l‐DOPA‐induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?

“…A recent study by Morales et al . () has suggested that occurrence of reactive astrocytosis needs the previous action of 6‐OHDA on dopaminergic neurons, in accord with the potentiation of LID by inflammagen LPS (Mulas et al ., ).…”

Neuroprotective Effects of Loganin on MPTP‐Induced Parkinson's Disease Mice: Neurochemistry, Glial Reaction and Autophagy Studies

“…In a study by Tambuyzer et al [] shows that inhibition of microglia over‐activation may represent a therapeutic target in alleviating the progression of neurodegenerative diseases. Striatal reactive astrocyte during the dopaminergic denervation probably is the first stages of PD [Morales et al, ]. And inhibition of astrocyte activation is proposed as a strategy for the treatment of PD [Liu et al, ].…”

The S100B story: from biomarker to active factor in neural injury

“…; Morales et al . ). S100B was over‐expressed in crucial brain regions such as substantia nigra and striatum both in PD patients (Sathe et al .…”

“…In the pathogenic mechanisms of PD, a crucial role has been indicated for activated pro-inflammatory astrocytes, also involving the overproduction and release of S100B, in response to striatal dopaminergic denervation or 6-hydroxydopamine administration Morales et al 2016). S100B was over-expressed in crucial brain regions such as substantia nigra and striatum both in PD patients (Sathe et al 2012;Rydbirk et al 2017) and in MPTP-treated mice (Sathe et al 2012;Viana et al 2016).…”