Histopathological Findings in the Striatum and Substantia Nigra in a Rat Model of Parkinson's Disease
Sergejs Isajevs, Darja Isajeva, Jolanta Pupure, Juris Rumaks, Simons Svirskis, Zane Dzirkale, Baiba Jansone, Vija Klusa. Faculty of Medicine, University of Latvia, Riga, Latvia
Background: Oxidative stress and neuroinflammation play a significant role in the pathogenesis of Parkinson's disease (PD), however the cause of the neuronal loss in PD is still poorly understood. The aim of present study was to evaluate the influence of 6-hydroxydopamine (6-OHDA) on the expression on inflammatory, neuroregenerative, as well as GABAergic and cholinergic pathways biomarkers by analyzing iNOS, IL-1β, GFAP, IBA-1, nestin, tyrosine hydroxylase, glutamate decarboxylase 65/67 (GAD65/67), acetylcholinesterase (AchE), c-jun/AP-1 and GAP-43 expression in the brain striatum and substantia nigra of animal model of Parkinson's disease (PD).
Design: PD was modeled by a single 6-OHDA intrastriatal injection in rats (20μg). Control group received artificial cerebrospinal fluid (aCSF). Rat brains were dissected on day 28 after discontinuation of 6-OHDA injections. The expression of iNOS, IL-1β, GFAP, IBA-1, nestin, tyrosine hydroxylase, glutamate decarboxylase 65/67 (GAD65/67), acetylcholinesterase (AChE), c-jun/AP-1 and GAP-43 was assessed immunohistochemically and by western blot in brain striatum and substantia nigra.
Results: The obtained results showed that 6-OHDA caused an increase in GAD65/67, IL-1β, iNOS and c-jun/AP-1 expression in rat striatum and substantia nigra (vs. control artificial CSF group). In addition, 6-OHDA increased the number of GFAP positive macroglial and IBA-1 positive microglial cells both in the striatum and substantia nigra. Obtained results showed that 6-OHDA decreased the number of AChE immunoreactive nerve fibers in striatum vs. control group (6 ± 2 vs. 23 ±4, p=0.03, fibers/mm2), however it tend to increase AChE expression in substantia nigra. Interestingly, 6-OHDA administration upregulated GAP-43 protein expression in rat striatum, but downregulated it in substantia nigra. Our study showed a tendency of increased nestin positive cells in the rat striatum in 6-OHDA lesioned striatum, however nestin expression was not observed in substantia nigra.
Conclusions: The obtained results showed multifaceted mechanisms in the pathogenesis of Parkinson's disease that involve inflammatory, neurodegenerative as glutamate/GABAergic and cholinergic pathways.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 280, Tuesday Afternoon