Brain Changes in Iron Loading Disorders
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Abnormal iron accumulation within the brain is associated with various neurodegenerative diseases; however, there is debate about whether milder disorders of systemic iron loading, such as haemochromatosis, affect the brain. Arguments on both sides of the debate are often based on some common assumptions that have not been rigorously tested by appropriate experimentation. Recent research from our lab has applied high-throughput molecular techniques such as microarray to models of dietary and genetic iron loading to identify subtle but important effects on molecular systems in the brain that may go undetected by other methods commonly used in the field. In this chapter, we review the existing research in animal models and human patients and discuss the strengths and limitations of the different approaches commonly used. Using our findings as an example, we argue that transcriptomic methods can provide unique insights into how systemic iron loading can affect the brain and suggest some basic guidelines for extracting the most robust and reliable information from microarray studies.
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Johnstone, D.; Graham, Ross; Trinder, D.; Delima, R.; Riveros, C.; Olynyk, John; Scott, R.; Moscato, P.; Milward, E. (2012)Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which ...
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric featuresHeidari, M.; Johnstone, D.; Bassett, B.; Graham, Ross; Chua, A.; House, M.; Collingwood, J.; Bettencourt, C.; Houlden, H.; Ryten, M.; Olynyk, John; Trinder, D.; Milward, E. (2016)The ‘neurodegeneration with brain iron accumulation’ (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with ...
Brain transcriptome perturbations in the transferrin receptor 2 mutant mouse support the case for brain changes in iron loading disorders, including effects relating to long-term depression and long-term potentiationAcikyol, B.; Graham, Ross; Trinder, D.; House, M.; Olynyk, John; Scott, R.; Milward, E; Johnstone, D. (2013)Iron abnormalities within the brain are associated with several rare but severe neurodegenerative conditions. There is growing evidence that more common systemic iron loading disorders such as hemochromatosis can also ...