Nutritional evaluation of Huntington disease patients

Morales, Luz Marina; Estévez, Jesús; Suárez, Héctor; Villalobos, Rafael; Bonilla, Leonor Chacín de; Bonilla, Ernesto

doi:10.1093/ajcn/50.1.145

Cited by 74 publications

(63 citation statements)

References 11 publications

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“…Despite differences in human and mouse metabolism the CAG expansion in transgenic R6/1 mice causes weight loss in line with that observed in human HD patients [52,53]. Consistent with previous reports we observed a milder weight loss phenotype in females compared to male R6/1 mice [54,55].…”

Section: Discussionsupporting

confidence: 92%

Brain Cholesterol Synthesis and Metabolism is Progressively Disturbed in the R6/1 Mouse Model of Huntington’s Disease: A Targeted GC-MS/MS Sterol Analysis

Kreilaus

Spiro

Hannan

et al. 2015

JHD

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. (2015). Brain cholesterol synthesis and metabolism is progressively disturbed in the R6/1 mouse model of Huntington's disease: a targeted GC-MS/MS sterol analysis. Journal of Huntington's Disease, 4 (4), 305-318.Brain cholesterol synthesis and metabolism is progressively disturbed in the R6/1 mouse model of Huntington' s disease: a targeted GC-MS/MS sterol analysis AbstractBackground:Cholesterol has essential functions in neurological processes that require tight regulation of synthesis and metabolism. Perturbed cholesterol homeostasis has been demonstrated in Huntington's disease, however the exact role of these changes in disease pathogenesis is not fully understood. Objective:This study aimed to comprehensively examine changes in cholesterol biosynthetic precursors, metabolites and oxidation products in the striatum and cortex of the R6/1 transgenic mouse model of Huntington's disease. We also aimed to characterise the progression of the physical phenotype in these mice. Methods:GC-MS/MS was used to quantify a broad range of sterols in the striatum and cortex of R6/1 and wild type mice at 6, 12, 20, 24 and 28 weeks of age. Motor dysfunction was assessed over 28 weeks using the RotaRod and the hind-paw clasping tests. Results:24(S)-Hydroxycholesterol and 27-hydroxycholesterol were the major cholesterol metabolites that significantly changed in R6/1 mice. These changes were specifically localised to the striatum and were detected at the end stages of the disease. Cholesterol synthetic precursors (lathosterol and lanosterol) were significantly reduced in the cortex and striatum by 6 weeks of age, prior to the onset of motor dysfunction, as well as the cognitive and affective abnormalities previously reported. Elevated levels of desmosterol, a substrate of delta(24)-sterol reductase (DHCR24), were also detected in R6/1 mice at the end time-point. Female R6/1 mice exhibited a milder weight loss and hind paw clasping phenotype compared to male R6/1 mice, however, no difference in the brain sterol profile was detected between sexes. Conclusion:Several steps in cholesterol biosynthetic and metabolic pathways are differentially altered in the R6/1 mouse brain as the disease progresses and this is most severe in the striatum. This provides further insights into early molecular mediators of HD onset and disease progression and identifies candidate molecular targets for novel therapeutic approaches.

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Section: Discussionsupporting

confidence: 92%

Brain Cholesterol Synthesis and Metabolism is Progressively Disturbed in the R6/1 Mouse Model of Huntington’s Disease: A Targeted GC-MS/MS Sterol Analysis

Kreilaus

Spiro

Hannan

et al. 2015

JHD

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“…[10][11][12] Concordance rates in MZ twins for diabetes mellitus 13 are 57% at 10 years and 76% at 15 years. In one study 14 of concordance in patients with rheumatoid arthritis, there was a zero concordance rate in MZ twins in a point prevalence study, implying a lack of significant genetic correlation. The differences between the twins in these medical aspects are, therefore, not surprising, and may or may not be linked to their different susceptibilities to the HD gene abnormality.…”

Section: Commentmentioning

confidence: 98%

Monozygotic Twins Discordant for Huntington Disease After 7 Years

Friedman¹,

Trieschmann²,

Myers³

et al. 2005

Arch Neurol

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Background: Huntington disease (HD) has only rarely been identified in identical twins. All described twins have had disease onset within 1 year of each other, suggesting that disease onset is determined solely by genetic influences.Objective: To describe a unique set of monozygotic twins in whom clinical HD onset is at least 7 years apart.Design: A 71-year-old woman was diagnosed as having HD based on medical history, physical examination results consistent with HD, and a CAG trinucleotide repeat number of 39 in the HD gene on chromosome 4. Her onset was 6 years earlier. Her genetically confirmed identical twin, carrying the same number of CAG repeats, was neurologically healthy when examined the next year. Only

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“…Some patients maintain the ability to feed themselves to a late Weight loss is a common and recognized feature throughout all stages of the disease [9][10][11] and its etiology remains uncertain. Its progressive nature is often marked in the later stages [9,12,13] of the disease and correlates with the CAG repeat number [14]. Evidence, including animal studies, suggests that there are several possible contributing factors, such as:…”

Section: Stages Of Hdmentioning

confidence: 99%

Nutritional Management of Individuals With Huntington’s Disease: Nutritional Guidelines

Brotherton

Campos

Rowell

et al. 2012

Neurodegen. Dis. Manage.

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SUMMARY The delivery of good nutritional care is a fundamental element of the management of individuals with Huntington’s disease and all patients with Huntington’s disease will, at some time, need dietary intervention because of the sequela of the disease; yet there are no European nutritional guidelines. The European Huntington’s Disease Network Standards of Care Dietitians Group has brought together expert dietitians from across Europe to produce nutritional guidelines to improve the nutritional management of individuals with Huntington’s disease. The guidelines were developed to promote optimal nutritional screening, assessment and management of individuals throughout all stages of the disease, with the aim of improving the standard of nutritional care delivered. Literature was systematically searched in an attempt to ensure that the recommendations are based on sound evidence and where evidence is lacking, specific guidance is based on consensus expert dietetic opinion. The provision of nutritional care varies widely between countries. Implementation of these nutritional guidelines across Europe should improve the quality of nutritional care delivered to individuals with Huntington’s disease.

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Nutritional evaluation of Huntington disease patients

Cited by 74 publications

References 11 publications

Brain Cholesterol Synthesis and Metabolism is Progressively Disturbed in the R6/1 Mouse Model of Huntington’s Disease: A Targeted GC-MS/MS Sterol Analysis

Brain Cholesterol Synthesis and Metabolism is Progressively Disturbed in the R6/1 Mouse Model of Huntington’s Disease: A Targeted GC-MS/MS Sterol Analysis

Monozygotic Twins Discordant for Huntington Disease After 7 Years

Nutritional Management of Individuals With Huntington’s Disease: Nutritional Guidelines

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