title: Intraventricular injection of 6-hydroxydopamine results in an increased number of tyrosine hydroxylase immune-positive cells in the rat cortex.
abstract: Previously we have demonstrated that intraventricular injection of 6-hydroxydopamine (6-OHDA) results in increased proliferation and de-differentiation of rat cortical astrocytes into progenitor-like cells 4 days after lesion (Wachter et al., 2010). To find out if these cells express tyrosine hydroxylase (TH), the rate-limiting enzyme in the catecholamine synthesis pathway, we performed immunohistochemistry in the rat cortex following intraventricular injection of 6-OHDA. Four days after injection we demonstrated a strong emergence of TH-positive (TH(+)) somata in the cortices of 6-OHDA-lesioned animals. The number of TH(+) cells in the cortex of 6-OHDA-lesioned animals was 15 times higher than in sham-operated animals, where virtually no TH(+) somata occurred. Combining TH immunohistochemistry with classical Nissl stain yielded complete congruency, and ∼45% of the TH(+) cells co-expressed calretinin, which indicates an interneuron affiliation. There was no co-staining of TH with other interneuron markers or with glial markers such as glial fibrillary acidic protein (GFAP) or the neural stem/progenitor marker Nestin, nor could we find co-localization with the proliferation marker Ki67. However, we found a co-localization of TH with glial progenitor cell markers (Sox2 and S100β) and with polysialylated-neural cell adhesion molecule (PSA-NCAM), which has been shown to be expressed in immature, but not recently generated cortical neurons. Taken together, this study seems to confirm our previous findings with respect to a 6-OHDA-induced expression of neuronal precursor markers in cells of the rat cortex, although the TH(+) cells found in this study are not identical with the potentially de-differentiated astrocytes described recently (Wachter et al., 2010). The detection of cortical cells expressing the catecholaminergic key enzyme TH might indicate a possible compensatory role of these cells in a dopamine-(DA)-depleted system. Future studies are needed to determine whether the TH(+) cells are capable of DA synthesis to confirm this hypothesis.
authors.affiliation: Graduate School of Cellular & Molecular Neuroscience, University of Tübingen, Österbergstrasse 3, 72047 Tübingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wachter
authors.affiliation: Institute of Neuroanatomy, University of Tübingen, Österbergstrasse 3, 72074 Tübingen, Germany; Graduate School of Cellular & Molecular Neuroscience, University of Tübingen, Österbergstrasse 3, 72047 Tübingen, Germany. Electronic address: sandro.caradonna@uni-tuebingen.de.
authors.forename: S
authors.initials: S
authors.lastname: Caradonna
authors.affiliation: Institute of Neuroanatomy, University of Tübingen, Österbergstrasse 3, 72074 Tübingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Gittinger
authors.affiliation: Institute of Neuroanatomy, University of Tübingen, Österbergstrasse 3, 72074 Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schläger
authors.affiliation: Institute of Neuroanatomy, University of Tübingen, Österbergstrasse 3, 72074 Tübingen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Küppers
mesh_terms: D000818:Animals; D064032:Calbindin 2 / Q000378:metabolism; D002452:Cell Count; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007395:Interneurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: C576512:Calb2 protein, rat; D064032:Calbindin 2; D039842:Neural Cell Adhesion Molecule L1; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D055748:SOXB1 Transcription Factors; D012794:Sialic Acids; C527784:Sox2 protein, rat; C103469:polysialyl neural cell adhesion molecule; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: Parkinson’s model; astrocytes; dopamine; immunohistochemistry; progenitor-like cells