Central and Peripheral proinflammatory stimuli exacerbate ongoing neurodegeneration in a Parkinson’s Disease (PD) Model

M.C. POTT GODOY; R. TARELLI;; C.C. FERRARI; F.J. PITOSSI

Madrid, España

Congreso; 2nd Iberoamerican Congress on Neuroimmunomodulation; 2007

PD is a neurodegenerative disorder characterized by the progressive loss of neurons from the substantia nigra (s.n.). One pathophysiological feature found in animal models and PD patients is brain inflammation, in particular, microglial activation (stage-2). Recent studies on the inflammation observed in other models of neurodegenerative diseases such as prion and Alzeimer´s disease showed that microglia seemed to be primed and can be re-activated upon peripheral proinflammatory stimulation. We have studied glial activation and profile of cytokine induction in a rat model of PD. We hypothesize that central or peripheral stimuli could exacerbate brain inflammation and the ongoing neurodegeneration, leading to an exacerbation of PD motor symptoms and disease progression. Rats previously injected with 6hydroxidopamine (6OHDA) in the striatum were then injected with bacterial lipopolysaccharide (LPS) in the s.n. or adenoviral vector producing human IL-1 beta intravenously as a proinflammatory stimulus. Contrary to controls, both animal groups revealed end-stage microglial activation (stage-4) in the sn. Significant exacerbation of neurodegeneration was observed in both models when the proinflammatory stimulus was present. The central stimulus significantly manifested earlier and exacerbating behavioural deficits and expression of IL-1 beta in s.n. For the first time we demonstrate that a non-degenerative stimulus whether central or peripheral produced an increase in 6-OHDA-mediated neurodegeneration, establishing that inflammation could be a risk factor for the progression of PD.