The Role of Inflammatory Mediators in Parkinson’s Neurodegeneration

This project investigates the role of inflammatory substances in the initiation and progression of the neurodegenerative process in typical idiopathic Parkinson’s disease. Support for the actions of these inflammatory mediators will be explored using evidence from human cerebrospinal fluid (CSF) and serum, human-derived cell cultures, and lipopolysaccharide (LPS) treated animal models. This grant proposal will take a multifaceted approach to understanding the initiation and progression of neurodegeneration in a number of cell populations and tissues, using different imaging techniques. This work is of critical and timely importance as the two most common neurodegenerative diseases, Alzheimer’s dementia and Parkinson’s disease, increase exponentially in prevalence with age. Furthermore, Parkinson’s disease is relentlessly progressive, ultimately impacting an individual’s functional ability and diminishing quality of life for themselves and their families. The project is a collaborative proposal involving expert investigators from the basic and clinical sciences at the University of Texas Health Science Center at Houston, that share a common goal of elucidating the cell death pathways in Parkinson related neurodegeneration. We will use patient CSF and serum collection and correlation with disease stage (Mya Schiess, Tammy Danielle), immunofluorescence of cell cultures and treated animals (Roger Bick, Brian Poindexter), markers and mechanisms in cell death pathways (Diane Bick, Roger Bick, and Brian Poindexter), tissue pathology (Marylee Kott) and markers of inflammation and organ failure (Marie-Francoise Doursout). We believe this work will provide new insights into the initiation and progression of Parkinson’s degeneration and further illustrate the role(s) of specific proteins in cellular dysfunction.

neurodegenerationGlial cells

Mya Schiess (UT-Neurology), Kha Dinh, Brian Poindexter, Roger Bick. Localization of tau protein (red) in cultured glial cells by deconvolution fluorescence microscopy.Reference – Bick, RJ, et al, Brain Research. 1217:203-212, 2008

 

ubiquitin-gliaUbiquitin in glial cells

Mya Schiess (UT-Neurology), Kha Dinh, Brian Poindexter, Roger Bick. Localization of ubiquitin (red) in cultured glial cells by deconvolution fluorescence microscopy.Reference – Bick, RJ et al. Brain Research. 1217:203-212, 2008.

 

agg-il-6-tau_13IL-6-Tau

Kha Dinh, Mya Schiess (UT-Neurology), Brian Poindexter, Roger Bick, 3D model of tau protein (red) in cultured glial cells, disrupted following treatment with the cytokine IL-6.

 

 

blood-vessels-brain-cortexBlood vessels in the brain cortex

Diana Hook, Brian Poindexter, Mya Schiess, Marylee Kott, Diane Bick, Marie-Francois Doursout, Kha Dinh, Roger Bick, Blood vessels (bright green) coursing through brain cortical tissue. Blue show nuclei.

 

auerbach-plexusAuerbach’s Plexus

Roger Bick, Gordon Klein (UTMB), Brian Poindexter, Myenteric plexus of small intestine stained for the calcium sensing receptor.

 

 

lps-induced-tau-aggregationLPS-induced Tau aggregation

Diana Hook, Brian Poindexter, Mya Schiess, Marylee Kott, Diane Bick, Marie-Francois Doursout, Kha Dinh, Roger Bick, Tau aggregation (yellow/red) in brain cortex following endotoxin treatment.

 

blood-vessels-substantia-nigraBlood vessels in substantia nigra

Diana Hook, Brian Poindexter, Mya Schiess, Marylee Kott, Diane Bick, Marie-Francois Doursout, Kha Dinh, Roger Bick, Blood vessels coursing through the highly nucleated substantia nigra of an LPS treated animal.

 

ubiquitin-glial-cellsUbiquitin in glial cells

Mya Schiess (UT-Neurology), Kha Dinh, Brian Poindexter, Roger Bick. Localization of ubiquitin (red) in cultured glial cells by deconvolution fluorescence microscopy.Reference – Bick, RJ, et al, Brain Research. 1217:203-212, 2008.

 

alpha-synucelin-gliaα-synucelin in glia

Kha Dinh, Mya Schiess (UT-Neurology), Brian Poindexter, Roger Bick, 3D model of alpha-synuclein (red) in cultured glial cells, disrupted following treatment with the cytokine gamma-interferon.

 

alpha-synucelin-gliaBrain cortex

Diana Hook, Brian Poindexter, Mya Schiess, Marylee Kott, Diane Bick, Marie-Francois Doursout, Kha Dinh, Roger Bick, Interleukin-1 beta (red) in cortex of LPS treated brain.

 

 

glial-cell-mitochondriaGlial cell mitochondria

Brian Poindexter, Kha Dinh, Mya Schiess, Roger Bick, Cultured glial cells probed for mitochondrial content (red-MitoTracker).

 

 

RBOL48LPSTNF04Cortex (rat)

Diana Hook, Brian Poindexter, Mya Schiess, Marylee Kott, Diane Bick, Marie-Francois Doursout, Kha Dinh, Roger Bick, TNF (red) in cortex of rat brain along a large arteriole (bright green/light blue)