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    Brain transcriptome perturbations in the Hfe -/- mouse model of genetic iron loading

    Access Status
    Fulltext not available
    Authors
    Johnstone, D.
    Graham, Ross
    Trinder, D.
    Delima, R.
    Riveros, C.
    Olynyk, John
    Scott, R.
    Moscato, P.
    Milward, E.
    Date
    2012
    Type
    Journal Article
    
    Metadata
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    Citation
    Johnstone, Daniel and Graham, Ross and Trinder, Debbie and Delima, Roheeth and Riveros, Carlos and Olynyk, John and Scott, Rodney and Moscato, Pablo and Milward, Elizabeth. 2012. Brain transcriptome perturbations in the Hfe -/- mouse model of genetic iron loading. Brain Research. 1448: pp. 144-152.
    Source Title
    Brain Research
    DOI
    10.1016/j.brainres.2012.02.006
    ISSN
    0006-8993
    URI
    http://hdl.handle.net/20.500.11937/40786
    Collection
    • Curtin Research Publications
    Abstract

    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 is usually caused by loss-of-function polymorphisms in the HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe-/-mice relative to wildtype AKR controls (age 10 weeks, n≥4/group). The Hfe-/- mouse brain showed numerous significant changes in transcript levels (p<0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients.

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