title: Knockdown of interleukin-1 receptor 1 is not neuroprotective in the 6-hydroxydopamine striatal lesion rat model of Parkinson's disease.
abstract: It is well established that neuroinflammation is associated with the progression of many neurodegenerative diseases, including Parkinson's disease (PD). Activated microglia and elevated levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) have been found in the brain and cerebrospinal fluid of PD patients, suggesting that IL-1β may be involved in the pathogenesis of this disease. This study aimed to knock down the expression of the interleukin-1 type 1 receptor (IL-1R1) to evaluate any potential therapeutic effect of limiting the action of IL-1β in the substantia nigra following a unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesion in rats. Adult Sprague-Dawley rats received intranigral injections of shRNA specific for IL-1R1, followed 2 weeks later by intrastriatal 6-OHDA. Injection of IL-1R1 shRNA did not prevent 6-OHDA-induced loss of motor function or loss of nigral dopamine neurons. IL-1R1 expression was increased in the midbrain following 6-OHDA injection; this effect was attenuated in 6-OHDA-treated animals that had received IL-1R1 shRNA. These data suggest that while IL-1R1 was increased in 6-OHDA-treated animals and reduced following shRNA injection, the neurodegeneration induced by 6-OHDA was not mediated through IL-1R1.
authors.affiliation: 1Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork , Cork , Ireland.
authors.forename: Sinéad
authors.initials: S
authors.lastname: Walsh
authors.forename: Aisling
authors.initials: A
authors.lastname: Gavin
authors.forename: Séan
authors.initials: S
authors.lastname: Wyatt
authors.forename: Catriona
authors.initials: C
authors.lastname: O'Connor
authors.forename: Karen
authors.initials: K
authors.lastname: Keeshan
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Nolan
authors.forename: Gerard W
authors.initials: GW
authors.lastname: O'Keeffe
authors.forename: Aideen M
authors.initials: AM
authors.lastname: Sullivan
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000662:Amphetamines; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D000662:Amphetamines; D034741:RNA, Small Interfering; D053573:Receptors, Interleukin-1 Type I; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: degeneration; dopaminergic neuron; neuroinflammation; shRNA