Abstract
Neuroinflammation is common in neurodegenerative diseases including Parkinson disease (PD). Expression of 25 mRNAs was assessed with TaqMan-PCR including members of the complement system, colony stimulating factors, Toll family, cytokines IL-8, IL-6, IL-6ST, IL-1B, TNF-α family, IL-10, TGFβ family, cathepsins and integrin family, in the substantia nigra pars compacta, putamen, frontal cortex area 8 and angular gyrus area 39, in a total of 43 controls and 56 cases with PD-related pathology covering stages 1-6 of Braak. Up-regulation of IL-6ST was the only change in the substantia nigra at stages 1-2. Down-regulation of the majority of members examined occurred in the substantia nigra from stage 4 onwards. However, region-dependent down- and up-regulation of selected mRNAs occurred in the putamen and frontal cortex, whereas only mRNA up-regulated mRNAs were identified in the angular cortex from stage 3 onwards in PD cases. Protein studies in frontal cortex revealed increased IL6 expression and reduced IL-10 with ELISA, and increased IL-6 with western blotting in PD. Immunohistochemistry revealed localization of IL-5, IL-6 and IL-17 receptors in glial cells, mainly microglia; IL-5, IL-10 and M-CSF in neurons; TNF-α in neurons and microglia; and active NF-κB in the nucleus of subpopulations of neurons and glial cells in PD. Distinct inflammatory responses, involving pro- and anti-inflammatory cytokines, and variegated mediators of the immune response occur in different brain regions at the same time in particular individuals. Available information shows that altered α-synuclein solubility and aggregation, Lewy body formation, oxidative damage and neuroinflammation converge in the pathogenesis of PD.