Knockdown of interleukin-1 receptor 1 is not neuroprotective in the 6-hydroxydopamine striatal lesion rat model of Parkinson's disease

Walsh, S., Gavin, A., Wyatt, S., O'Connor, C., Keeshan, K. , Nolan, Y. M., O'Keeffe, G. W. and Sullivan, A. M. (2014) Knockdown of interleukin-1 receptor 1 is not neuroprotective in the 6-hydroxydopamine striatal lesion rat model of Parkinson's disease. International Journal of Neuroscience, 125(1), pp. 70-77. (doi:10.3109/00207454.2014.904304)

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Publisher's URL: http://dx.doi.org/10.3109/00207454.2014.904304

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Keeshan, Dr Karen
Authors: Walsh, S., Gavin, A., Wyatt, S., O'Connor, C., Keeshan, K., Nolan, Y. M., O'Keeffe, G. W., and Sullivan, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:International Journal of Neuroscience
Publisher:Informa Healthcare
ISSN:0020-7454
ISSN (Online):1543-5245
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