Altered expression patterns of inflammation-associated and trophic molecules in substantia nigra and striatum brain samples from Parkinson’s disease, incidental Lewy body disease and normal control cases

Frontiers in Neuroscience. 2016;9 DOI 10.3389/fnins.2015.00507

 

Journal Homepage

Journal Title: Frontiers in Neuroscience

ISSN: 1662-4548 (Print); 1662-453X (Online)

Publisher: Frontiers Media S.A.

LCC Subject Category: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry

Country of publisher: Switzerland

Language of fulltext: English

Full-text formats available: PDF, HTML, ePUB, XML

 

AUTHORS

Douglas Gordon Walker (Arizona State University)
Lih-Fen eLue (Arizona State University)
Geidy eSerrano (Banner Sun Health Research Institute)
Thomas Gerald Beach (Banner Sun Health Research Institute)
Lucia eSue (Banner Sun Health Research Institute)
Charles H. Adler (Mayo Clinic College of Medicine)
John eCaviness (Mayo Clinic College of Medicine)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 14 weeks

 

Abstract | Full Text

Evidence of inflammation has been consistently associated with pathology in Parkinson’s disease (PD)-affected brains, and has been suggested as a causative factor. Dopaminergic neurons in the substantia nigra (SN) pars compacta, whose loss results in the clinical symptoms associated with PD, are particularly susceptible to inflammatory damage and oxidative stress. Inflammation in the striatum, where SN dopaminergic neurons project, is also a feature of PD brains. It is not known whether inflammatory changes occur first in striatum or SN. Many animal models of PD have implicated certain inflammatory molecules with dopaminergic cell neuronal loss; however, there have been few studies to validate these findings by measuring the levels of these and other inflammatory factors in human PD brain samples. This study also included samples from incidental Lewy body disease (ILBD) cases, since ILBD is considered a non-symptomatic precursor to PD, with subjects having significant loss of tyrosine hydroxylase-producing neurons. We hypothesized that there may be a progressive change in key inflammatory factors in ILBD samples intermediate between neurologically normal and PD. To address this, we used a quantitative antibody-array platform (Raybiotech-Quantibody arrays) to measure the levels of 160 different inflammation-associated cytokines, chemokines, growth factors, and related molecules in extracts of SN and striatum from clinically and neuropathologically characterized PD, ILBD and normal control cases. Patterns of changes in inflammation and related molecules were distinctly different between SN and striatum. Our results showed significantly different levels of interleukin (IL)-5, IL-15, monokine induced by gamma interferon, and IL-6 soluble receptor in SN between disease groups. A different panel of 13 proteins with significant changes in striatum, with IL-15 as the common feature, was identified. Although the ability to detect some proteins was limited by sensitivity, patterns of expression indicated involvement of certain T-cell cytokines, vascular changes and loss of certain growth factors, with disease progression. The results demonstrate the feasibility of profiling inflammatory molecules using diseased human brain samples, and have provided additional targets to validate in relation to PD pathology.