Dataset Information

Impaired Levels of Gangliosides in the Corpus Callosum of Huntington Disease Animal Models.

ABSTRACT: Huntington Disease (HD) is a genetic neurodegenerative disorder characterized by broad types of cellular and molecular dysfunctions that may affect both neuronal and non-neuronal cell populations. Among all the molecular mechanisms underlying the complex pathogenesis of the disease, alteration of sphingolipids has been identified as one of the most important determinants in the last years. In the present study, besides the purpose of further confirming the evidence of perturbed metabolism of gangliosides GM1, GD1a, and GT1b the most abundant cerebral glycosphingolipids, in the striatal and cortical tissues of HD transgenic mice, we aimed to test the hypothesis that abnormal levels of these lipids may be found also in the corpus callosum white matter, a ganglioside-enriched brain region described being dysfunctional early in the disease. Semi-quantitative analysis of GM1, GD1a, and GT1b content indicated that ganglioside metabolism is a common feature in two different HD animal models (YAC128 and R6/2 mice) and importantly, demonstrated that levels of these gangliosides were significantly reduced in the corpus callosum white matter of both models starting from the early stages of the disease. Besides corroborating the evidence of aberrant ganglioside metabolism in HD, here, we found out for the first time, that ganglioside dysfunction is an early event in HD models and it may potentially represent a critical molecular change influencing the pathogenesis of the disease.

SUBMITTER: Di Pardo A

PROVIDER: S-EPMC5052274 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Impaired Levels of Gangliosides in the Corpus Callosum of Huntington Disease Animal Models.

Di Pardo Alba A Amico Enrico E Maglione Vittorio V

Frontiers in neuroscience 20161006

Huntington Disease (HD) is a genetic neurodegenerative disorder characterized by broad types of cellular and molecular dysfunctions that may affect both neuronal and non-neuronal cell populations. Among all the molecular mechanisms underlying the complex pathogenesis of the disease, alteration of sphingolipids has been identified as one of the most important determinants in the last years. In the present study, besides the purpose of further confirming the evidence of perturbed metabolism of gan ...[more]

PMID: 27766070

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Project description:The Corpus Callosum (CC) is an important structure that includes the majority of fibers connecting the two brain hemispheres. Several neurodegenerative diseases may alter CC size and morphology leading to its atrophy and malfunction which may play a role in the pathological manifestations found in these diseases. The purpose of the current study is to determine any possible changes in CC size in patients suffering from Alzheimer's disease. The Study also investigated the effect of acetylcholinesterase inhibitors (AChEIs) on the size of CC and its association with improvement in the Alzheimer disease severity scores. Midsagittal size of CC were recorded prospectively from 439 routine T1-weighted MRI brain images in normal individuals. The internal skull surface was measured to calculate CC/ internal skull surface ratio. Two groups of patients were studied: 300 (150 male / 150 female) were healthy subjects and 130 (55 males / 75 females) had Alzheimer disease. Out of the 130 Alzheimer disease pateints, 70 patients were treated with Donepezil or Rivastigmine or both. The size of the CC was measured based on T1-weighted MRI images after the treatment to investigate any possible improvement in CC size. The mean surface area of CC in controls was 6.53±1.105 cm2. There was no significant difference between males and females (P < 0.627), and CC/ internal skull surface ratio was 4.41±0.77%. Patients with mild or severe Alzheimer disease showed a significant reduction in CC size compared to healthy controls. Treating mild Alzheimer patients with either Donepezil or Rivastigmine exerts a comparable therapeutic effect in improving the CC size. There was more improvement in the size of CC in patients with severe Alzheimer disease by using combined therapy of Donepezil and Rivastigmine than using single a medication. we measured the mean size of the various portions of the corpus callosum in normal individuals and Alzheimer patients before and after taking Donepezil and Rivastigmine. Alzheimer patients have pronounced reduction in CC which is corrected after taking Donepezil and Rivastigmine leading to remarkable improvement in Alzheimer disease severity scores.

Dataset Information

Impaired Levels of Gangliosides in the Corpus Callosum of Huntington Disease Animal Models.

Publications

Impaired Levels of Gangliosides in the Corpus Callosum of Huntington Disease Animal Models.

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