title: Re-expression of glia-derived nexin/protease nexin 1 depends on mode of lesion-induction or terminal degeneration: observations after excitotoxin or 6-hydroxydopamine lesions of rat substantia nigra.
abstract: The serine protease inhibitor and neurite outgrowth promoter glia derived nexin (GDN) is expressed in the rat CNS during embryogenesis and persists in the olfactory system of the adult where receptor neurons are replaced throughout life. We investigated whether GDN-immunoreactivity also appears in the adult at sites of synaptic rearrangement following nerve cell death and anterograde terminal degeneration in experimental models for Parkinson's disease. Rat substantia nigra was unilaterally lesioned by stereotaxic application of different toxins: 6-hydroxydopamine, which selectively destroys dopaminergic neurons, the excitotoxic glutamate analog ibotenic acid, or the glutamate receptor agonists N-methyl-D-aspartate and quisqualate, which cause circumscript lesions of the whole substantia nigra. Nerve cell death and astroglial reactivity were monitored by parallel cresyl staining and immunocytochemistry for glial fibrillary acidic protein, at survival times ranging from 2 to 100 days. Sustained de novo synthesis of GDN occurred in the dopamine depleted caudate putamen following excitotoxin or 6-hydroxydopamine induced degeneration of the substantia nigra and of the nigrostriatal pathway provided that the lesions were nearly complete. This is consistent with compensatory changes occurring in deafferented caudate putamen and suggests a permissive role of GDN in neuronal plasticity. In the substantia nigra astroglia exhibited GDN-immunoreactivity following excitotoxin injection but not after application of 6-hydroxydopamine. Thus differences in action mechanisms of neurotoxins may have distinct consequences on the astrocyte mediated response of the same affected brain region.
authors.affiliation: Section of Neuroanatomy, Basel University, Switzerland.
authors.forename: A L
authors.initials: AL
authors.lastname: Scotti
authors.forename: D
authors.initials: D
authors.lastname: Monard
authors.forename: C
authors.initials: C
authors.lastname: Nitsch
mesh_terms: D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000276:immunology; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007051:Ibotenic Acid / Q000633:toxicity; D007150:Immunohistochemistry; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D009410:Nerve Degeneration / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D058255:Protease Nexins; D011699:Putamen / Q000166:cytology / Q000502:physiology; D016318:Quisqualic Acid / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D017470:Receptors, Glutamate; D007051:Ibotenic Acid; D016202:N-Methylaspartate; D016627:Oxidopamine; D016318:Quisqualic Acid; D014446:Tyrosine 3-Monooxygenase