title: Glial overexpression of heme oxygenase-1: a histochemical marker for early stages of striatal damage.
abstract: The level of heme oxygenase-1 (HO-1) in the normal striatum is below the limit of immunodetection. However, HO-1 is overexpressed in both neural and non-neural cells in response to a wide range of lesions. We induced different types of lesions affecting the striatal cells or the main striatal afferent systems in rats to investigate if overexpression of HO-1 could be a useful histochemical marker of striatal damage. Thirty-six hours after intrastriatal or intraventricular injection of excitotoxins that affect striatal neurons (ibotenic acid) or of neurotoxins that affect striatal dopaminergic (6-hydroxydopamine) or serotonergic (5,7-dihydroxytriptamine) afferent terminals, or after surgical lesioning of cortico-striatal projections, there was intense induction of striatal HO-1 immunoreactivity (HO-1-ir). Double immunolabeling revealed that the HO-1-ir was located in glial cells. After intrastriatal injection of ibotenic acid, a central zone of neuronal degeneration contained numerous round and pseudopodic HO-1-ir cells, and was surrounded by a ring of HO-1-ir cells, most of which were immunoreactive for astroglial markers. Intraventricular injection of neurotoxins induced astroglial HO-1-ir cells which were more evenly distributed throughout the lesioned or denervated areas. HO-1-ir microglial cells were also observed in areas subjected to mechanical damage. The HO-1-ir was markedly lower or absent 1 week after lesion, and even more so 3 weeks after, although some HO-1-ir cells were still observed after intrastriatal injection of ibotenic acid or surgical corticostriatal deafferentation. The results indicate that determination of glial HO-1-ir is a useful histochemical marker for early stages of striatal damage.
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Muñoz
authors.forename: Pablo
authors.initials: P
authors.lastname: Rey
authors.forename: Juan
authors.initials: J
authors.lastname: Parga
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Guerra
authors.forename: Jose L
authors.initials: JL
authors.lastname: Labandeira-Garcia
mesh_terms: D015116:5,7-Dihydroxytryptamine; D000344:Afferent Pathways / Q000293:injuries / Q000601:surgery; D000818:Animals; D001253:Astrocytes / Q000201:enzymology; D001480:Basal Ganglia Diseases / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers; D003342:Corpus Striatum / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D003714:Denervation; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005911:Gliosis / Q000175:diagnosis / Q000201:enzymology / Q000473:pathology; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006419:Heme Oxygenase (Decyclizing); D007051:Ibotenic Acid; D007150:Immunohistochemistry; D017628:Microglia / Q000201:enzymology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D009457:Neuroglia / Q000201:enzymology* / Q000473:pathology; D009498:Neurotoxins; D016627:Oxidopamine; D010105:Oxygenases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006360:Heat-Shock Proteins; D009498:Neurotoxins; D007051:Ibotenic Acid; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D016627:Oxidopamine; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D004298:Dopamine