ABSTRACT This study was performed to examine cytokines and Parkinson’s disease (PD) associated proteins in brains of a rat lipopolysaccharide (LPS) model using fluorescence microscopy for quantifying and identifying locations of cytokines and neurodegenerative proteins. Rats were treated with LPS and organs were removed for determinations of nitric oxide (NO) content. Brain was sectioned and fluorescence deconvolution microscopy was used to localize both Parkinson’s disease-associated proteins and cytokines. Quantities were determined. NO levels increased in many tissues, including brain. Fluorescence labeling revealed double staining of cells for interleukin-6 and tau protein. Vascular endothelium labeled for both tumor necrosis-alpha (TNF) and ubiquitin. Many immune cells were visible in LPS brains, suggesting an inflammatory episode preceded migration of cytokine producing cells from the circulation and cerebrospinal fluid, initiating a neurodegenerative cascade in susceptible cells, while predisposing them to succumb to subsequent inflammatory episodes. Inflammatory cells and cytokines were seen in perivascular areas, associated with meninges, and concentrated between the olfactory bulb and cortex, indicating the likelihood of specific interactions with specific cells. TNF and glial cell line-derived neurotrophic factor (GDNF) showed a modest, sustained increase, while IL-1β and IL-10 exhibited abrupt, rapid increases, followed by sharp decreases. Results suggest that a gradual decline in neuronal sustainability occurs, with subsequent assaults initiating a protective mode that is overcome, and this gradual decline might describe the long term process of PD, with neurons becoming targeted by pro-inflammatory cytokines, protein aggregations and loss of the ubiquitin-proteasome recycling pathway late in the process.
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