Increased Nigral Iron Content and Alterations in Other Metal Ions Occurring in Brain in Parkinson's Disease

Abstract

Levels of iron, copper, zinc, manganese, and lead were measured by inductively coupled plasma spectroscopy in parkinsonian and age-matched control brain tissue. There was 31-35% increase in the total iron content of the parkinsonian substantia nigra when compared to control tissue. In contrast, in the globus pallidus total iron levels were decreased by 29% in Parkinson's disease. There was no change in the total iron levels in any other region of the parkinsonian brain. Total copper levels were reduced by 34-45% in the substantia nigra in Parkinson's disease; no difference was found in the other brain areas examined. Zinc levels were increased in substantia nigra in Parkinson's disease by 50-54%, and the zinc content of the caudate nucleus and lateral putamen was also raised by 18-35%. Levels of manganese and lead were unchanged in all areas of the parkinsonian brain studied when compared to control brains, except for a small decrease (20%) in manganese content of the medial putamen. Increased levels of total iron in the substantia nigra may cause the excessive formation of toxic oxygen radicals, leading to dopamine cell death.

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

“…PD is a neurodegenerative disorder characterized by the progressive death of neurons in the SN pars compacta, with accumulation of -synuclein, formation of Lewy bodies, intensive reactive gliosis and functional decay of the nigro-striatal circuitry (Zecca et al 2004). The hypothesis of an increase of iron in the SN of patients is generally accepted and documented (Sofic et al 1988;Dexter et al 1989;Oakley et al 2007), even though the difference between controls and PD samples appears to be affected by factors such as disease severity, gender or age of onset (Snyder and Connor 2009). Less clear are the modification of ferritin levels, with studies showing an increase (Sofic et al 1988;Licker et al 2014), a decrease (Dexter et al 1990;Connor et al 1995;Faucheux et al 2002) or changes in the relative H/L ratio (Koziorowski et al 2007), with consequent functional implication for iron handling.…”

Serum uric acid levels in Parkinson's disease and related disorders

“…Reactive oxygen species and oxidative stress may contribute to the pathogenesis of PD (Jenner & Olanow, 1996). Postmortem analyses of the brains of PD patients have reported increased iron levels as well as altered levels of other metal ions (Dexter et al., 1989). UA exerts antioxidant effects in neurons by acting as a scavenger of free radicals and as an iron chelator (Glantzounis, Tsimoyiannis, Kappas, & Galaris, 2005; Schlesinger & Schlesinger, 2008).…”

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…Neuromelanin appears to result from the autoxidation of dopamine, in a process that generates reactive oxygen species (ROS) [100] The presence of high amounts of iron in PD SN [101], which contribute to the production of free radicals via the Fenton-Haber Weiss reaction, has also been pointed out as a cause for selective degeneration of these neurons. In this reaction, hydrogen peroxide (H 2 O 2 ) generated during normal metabolism, during electron transport in mitochondria, or by pathogenic mechanisms can be subsequently converted to the extremely toxic hydroxyl radical ( d OH), which may elicit cellular damage, lipid peroxidation, and eventually apoptosis [102].…”