Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications.

Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Research Abstract Details 

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Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Abstract Text:

George Bartzokis,Po H Lu,Todd A Tishler,Sophia M Fong,Bolanle Oluwadara,J Paul Finn,Danny Huang,Yvette Bordelon,Jim Mintz,Susan Perlman,

BACKGROUND: Postmortem and in vivo imaging data support the hypothesis that premature myelin breakdown and subsequent homeostatic remyelination attempts with increased oligodendrocyte and iron levels may contribute to Huntington's Disease (HD) pathogenesis and the symmetrical progress of neuronal loss from earlier-myelinating striatum to later-myelinating regions. A unique combination of in vivo tissue integrity and iron level assessments was used to examine the hypothesis. METHODS: A method that uses two Magnetic resonance imaging (MRI) instruments operating at different field-strengths was used to quantify the iron content of ferritin molecules (ferritin iron) as well as tissue integrity in eight regions in 11 HD and a matched group of 27 healthy control subjects. Three white matter regions were selected based on their myelination pattern (early to later-myelinating) and fiber composition. These were frontal lobe white matter (Fwm) and splenium and genu of the corpus callosum (Swm and Gwm). In addition, gray matter structures were also chosen based on their myelination pattern and fiber composition. Three striatum structures were assessed [caudate, putamen, and globus pallidus (C, P, and G)] as well as two comparison gray matter regions that myelinate later in development and are relatively spared in HD [Hippocampus (Hipp) and Thalamus (Th)]. RESULTS: Compared to healthy controls, HD ferritin iron levels were significantly increased in striatum C, P, and G, decreased in Fwm and Gwm, and were unchanged in Hipp, Th, and Swm. Loss of tissue integrity was observed in C, P, Fwm, and especially Swm but not Hipp, Th, G, or Gwm. This pattern of findings was largely preserved when a small subset of HD subjects early in the disease process was examined. CONCLUSIONS: The data suggest early in the HD process, myelin breakdown and changes in ferritin iron distribution underlie the pattern of regional toxicity observed in HD. Prospective studies are needed to verify myelin breakdown and increased iron levels are causal factors in HD pathogenesis. Tracking the effects of novel interventions that reduce myelin breakdown and iron accumulation in preclinical stages of HD could hasten the development of preventive treatments.

Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Publishing Authors By Initials

G Bartzokis,PH Lu,TA Tishler,SM Fong,B Oluwadara,JP Finn,D Huang,Y Bordelon,J Mintz,S Perlman,

For similar nervous system: neuroglia: oligodendroglia: myelin sheath research abstracts see: nervous system: neuroglia: oligodendroglia: myelin sheath research

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Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Neurochemical research

VOLUME: 32

Page Numbers: 1655-64

Journal Abbreviation: Neurochem. Res.

ISSN: 0364-3190

DAY: 5

MONTH: 05

YEAR: 2007

Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7613461

Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Keywords Mesh Terms:

KEYWORDS: Myelin Sheath

MESH TERMS: pathology

Chemical & Substance for Abstract: Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications. Information

Substance Name: Ferritins

Registry Number: 9007-73-2

Grant and Affiliation Information for Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications.

AFFILIATION: Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. gbar@ucla.edu

Country: United States

AGENCY: United States NIMH

GRANT: MH6357-01A1

ACRONYM: MH

MEDLINETA: Neurochem Res

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