Microglial activation with atypical proinflammatory cytokine expression in a rat model of Parkinson's disease
- 25 November 2003
- journal article
- research article
- Published by Wiley in European Journal of Neuroscience
- Vol. 18 (10) , 2731-2742
- https://doi.org/10.1111/j.1460-9568.2003.03014.x
Abstract
Microglial activation has been associated with the pathogenesis of Parkinson's disease (PD). Among the many components of this reaction, cytokines have been proposed as candidates to mediate neurodegenerative or neuroprotective effects. We investigated the interleukin‐1 system and tumour necrosis factor‐α mRNA and protein levels at different time intervals in the subacute intrastriatal 6‐hydroxydopamine rat model of PD, in parallel with the inflammatory response. Immunohistochemistry showed that microglial cells were activated from days 6–30 postlesion in the substantia nigra pars compacta. This microglial activation was accompanied by an atypical proinflammatory cytokine production: Interleukin‐1α and β mRNAs were found to be elevated 30 days post‐6‐hydroxydopamine injection (2‐ and 16‐fold, respectively), but no induction for interleukin‐1α or β at the protein level was detected by ELISA. As a control, a classical proinflammatory stimulus, namely endotoxin, was capable of inducing these cytokines at similar mRNA levels but also at the protein level. In addition, tumour necrosis factor‐α mRNA was hardly or not detected in the substantia nigra at any time point studied. Our data point out a tight control of key proinflammatory cytokine production in our model of PD. This work supports the notion that chronic neuronal death per se does not induce secretion of these proinflammatory cytokines but that an additional stimulus is necessary to stimulate proinflammatory cytokine production. The production of proinflammatory cytokines from “primed” microglia may in turn modulate disease progression as has been recently proposed in a model of prion disease.Keywords
This publication has 48 references indexed in Scilit:
- Modeling Parkinson's Disease in Rats: An Evaluation of 6-OHDA Lesions of the Nigrostriatal PathwayExperimental Neurology, 2002
- Atypical inflammation in the central nervous system in prion diseaseCurrent Opinion in Neurology, 2002
- Experimental models of Parkinson's diseaseNature Reviews Neuroscience, 2001
- The Inflammation Hypothesis of AgingAnnals of the New York Academy of Sciences, 2001
- Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.Journal of Clinical Investigation, 1998
- Prognosis of Parkinson’s Disease in JapanEuropean Neurology, 1997
- Microglia: a sensor for pathological events in the CNSTrends in Neurosciences, 1996
- Interleukin-1β, interleukin-6, epidermal growth factor and transforming growth factor-α are elevated in the brain from parkinsonian patientsNeuroscience Letters, 1994
- Cause of Death in Alzheimer's DiseaseAge and Ageing, 1990
- Interleukin 1 of the central nervous system is produced by ameboid microglia.The Journal of Experimental Medicine, 1986