title: Intranigral infusion of interleukin-1beta activates astrocytes and protects from subsequent 6-hydroxydopamine neurotoxicity.
abstract: Activation of glial cells is a prevalent response to neuronal damage in brain disease and ageing, with potential neuroprotective and neurotoxic consequences. We were interested in studying the role of glial activation on dopaminergic neurons of the substantia nigra in an animal model of Parkinson's disease. Thus, we evaluated the effect of a pre-existing glial activation on the dopaminergic neuronal death induced by striatal infusion of 6-hydroxydopamine. We established a model of local glial activation by stereotaxic infusion of interleukin-1beta in the substantia nigra of adult rats. Interleukin-1beta (20 ng) induced a marked activation of astrocytes at days 2, 5 and 10, revealed by heat-shock protein 27 and glial fibrillary acid protein immunohistochemistry, but did not affect the microglial markers OX-42 and heat-shock proteins 32 or 47. Intranigral infusion of interleukin-1beta 5 days before a striatal injection of 6-hydroxydopamine significantly protected nigral dopaminergic cell bodies, but not striatal terminals from the 6-hydroxydopamine lesion. Also, in the animals pre-treated with interleukin-1beta, a significant prevention of 6-hydroxydopamine-induced reduction of adjusting steps, but not of 6-hydroxydopamine-induced amphetamine rotations, were observed. These data show the characterization of a novel model of local astroglial activation in the substantia nigra and support the hypothesis of a neuroprotective role of activated astrocytes in Parkinson's disease.
authors.affiliation: Experimental Neurology Laboratory, Neurological Service, Fundació Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Saura
authors.forename: Mireia
authors.initials: M
authors.lastname: Parés
authors.forename: Jordi
authors.initials: J
authors.lastname: Bové
authors.forename: Susana
authors.initials: S
authors.lastname: Pezzi
authors.forename: Jordi
authors.initials: J
authors.lastname: Alberch
authors.forename: Concepció
authors.initials: C
authors.lastname: Marin
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: María José
authors.initials: MJ
authors.lastname: Martí
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007263:Infusions, Parenteral; D007375:Interleukin-1 / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: D005904:Glial Fibrillary Acidic Protein; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D007375:Interleukin-1; D009363:Neoplasm Proteins; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase