A Nurr1 Agonist Causes Neuroprotection in a Parkinson’s Disease Lesion Model Primed with the Toll-Like Receptor 3 dsRNA Inflammatory Stimulant Poly(I:C)
Fig 2
SA00025 caused neuroprotection in the 6-OHDA lesion model primed with dsRNA inflammatory stimulant (poly(I:C)).
Rats received an initial unilateral injection of poly(I:C) in the SN (Start—day 0) and a subsequent unilateral injection of 6-OHDA in the striatum (day 12) (A). Rats were also administered daily with the Nurr1 agonist (30mg/kg/ day) or vehicle treatment throughout the paradigm (day 1–32) and were sacrificed at day 33 (A). 24 hrs following the last gavage treatment levels of the compound were significantly elevated in brain homogenates and was absent in vehicle treated conditions (B). Representative photomicrographs indicate the Nurr1 agonist caused a protective affect on TH +ve (brown) and NeuN +ve (grey) neurons within the SNpc and TH +ve fibers in the striatum (C). Rats had a significant sparing of dopaminergic neurons in the SNpc after 32 days of treatment with the compound, compared to vehicle treatment (D). Dopamine neuron fibers in the rostral striatum were also significantly spared with Nurr1 agonist treatment compared to vehicle treatment (E). Significance is annotated as p<0.05*, unpaired T-tests. N = 6–8/ group. Graphs are expressed at mean ± SEM. Abbreviations: dorsal lateral striatum (DL Stri) & medial striatum (M Stri). Scale bars = 200μm. TH and NeuN +ve neurons are indicated by black arrow heads and NeuN +ve neurons are indicated by grey arrows.