Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features

M. Heidari, D.M. Johnstone, B. Bassett, R.M. Graham, A. C. G. Chua, M. J. House, J.F. Collingwood, C. Bettencourt, H. Houlden, M. Ryten, J. K. Olynyk, D. Trinder, E.A. Milward

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Abstract

© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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 disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe -/- × Tfr2 mut brain (P=0.002, n =5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.
Original languageEnglish
Pages (from-to)1599-1607
JournalMolecular Psychiatry
Volume21
Issue number11
Early online date5 Jan 2016
DOIs
Publication statusPublished - Nov 2016

Fingerprint

Myelin Sheath
Rare Diseases
Iron
Brain
Transferrin Receptors
Hemochromatosis
Psychiatry
Atomic Spectrophotometry
Behavioral Symptoms
Regulator Genes
Ferritins
Reverse Transcription
Western Blotting
Staining and Labeling
Light
Polymerase Chain Reaction
Peptides
Neurodegeneration with brain iron accumulation (NBIA)
Proteins

Cite this

Heidari, M. ; Johnstone, D.M. ; Bassett, B. ; Graham, R.M. ; Chua, A. C. G. ; House, M. J. ; Collingwood, J.F. ; Bettencourt, C. ; Houlden, H. ; Ryten, M. ; Olynyk, J. K. ; Trinder, D. ; Milward, E.A. / Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features. In: Molecular Psychiatry. 2016 ; Vol. 21, No. 11. pp. 1599-1607.
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abstract = "{\circledC} 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.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 disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe -/- × Tfr2 mut brain (P=0.002, n =5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.",
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Heidari, M, Johnstone, DM, Bassett, B, Graham, RM, Chua, ACG, House, MJ, Collingwood, JF, Bettencourt, C, Houlden, H, Ryten, M, Olynyk, JK, Trinder, D & Milward, EA 2016, 'Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features' Molecular Psychiatry, vol. 21, no. 11, pp. 1599-1607. https://doi.org/10.1038/mp.2015.192

Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features. / Heidari, M.; Johnstone, D.M.; Bassett, B.; Graham, R.M.; Chua, A. C. G.; House, M. J.; Collingwood, J.F.; Bettencourt, C.; Houlden, H.; Ryten, M.; Olynyk, J. K. ; Trinder, D.; Milward, E.A.

In: Molecular Psychiatry, Vol. 21, No. 11, 11.2016, p. 1599-1607.

Research output: Contribution to journalArticle

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AU - Heidari, M.

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AU - Milward, E.A.

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N2 - © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.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 disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe -/- × Tfr2 mut brain (P=0.002, n =5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

AB - © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.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 disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe -/- × Tfr2 mut brain (P=0.002, n =5/group), primarily localized by Perls' staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P0.05). Overlap (P0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.

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