The history of the research of iron in parkinsonian substantia nigra

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NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - SHORT COMMUNICATION

The history of the research of iron in parkinsonian substantia nigra Andrzej Friedman • Jolanta Galazka-Friedman

Received: 10 June 2012 / Accepted: 21 August 2012 / Published online: 2 September 2012 Ó The Author(s) 2012. This article is published with open access at Springerlink.com

Abstract The role of iron in pathogenesis of Parkinson’s disease is widely discussed in the literature. The authors present the history of studies of iron in parkinsonian tissue from the substantia nigra. Keywords

Iron  Parkinson’s disease  Ferritin

Iron in the brain has already been investigated in the nineteenth century. In 1886 a study on iron content in the human brain by Dr. Zaleski was published (Zaleski 1886). This author suggested that iron present in the brain is not hemoglobin bound but bound to another type of protein. Almost 40 years later, Spatz discovered high concentration of iron in ‘‘extrapyramidal centers of human brain’’ such as, among others, substantia nigra (SN) (Spatz 1922). In 1924 Lhermitte et al., using Perls and Turnbull staining, described an increase of the concentration of iron in globus pallidus of one patient who died with the clinical diagnosis of Parkinson’s disease (PD). Concerning the iron in SN these authors wrote explicitly that ‘‘[iron] in the substantia nigra was present in normal amounts’’ (Lhermitte et al. 1924). This paper is often erroneously cited as the first description of an increase in the concentration of iron in parkinsonian SN. The quantitative studies of iron in human midbrain started with the paper by Hallgren and Sourander (1958). A. Friedman (&) Department of Neurology, Medical University of Warsaw, Warsaw, Poland e-mail: [email protected] J. Galazka-Friedman Faculty of Physics, Warsaw University of Technology, Warsaw, Poland

These authors assessed the concentration of total iron in 52 samples of human SN obtained from normal subjects. They used colorimetry and the concentration of iron in the whole SN was 184.6 ± 65.2 lg/g wet tissue (Hallgren and Sourander 1958). The first study aimed at the comparison of iron concentration in parkinsonian and control SN was that by Earle, who used X-ray fluorescent spectroscopy (Earle 1968). He examined 11 samples of parkinsonian SN obtained from formalin fixed brains and compared them to unknown number of control samples. It is important to note that the brain bank, from which he obtained the brains, kept them for extremely long time (some of them since 1862) in formalin. According to this author, the concentration of iron in parkinsonian samples was two times higher than that of control. It was only after 20 years that the first study quantitatively comparing the concentration of iron in parkinsonian SN and control was published (Sofic et al. 1988). These authors used spectrophotometry applied on small samples of 50–80 mg (eight parkinsonian and eight controls), which were pretreated by hydrochloric acid and pepsin before measurements. The concentration of ir