Alterations of membrane lipids and in gene expression of ganglioside metabolism in different brain structures in a mouse model of mucopolysaccharidosis type I (MPS I)
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- 作者：Fern ; o Kreutz ; Fern ; a dos Santos Petry ; Melissa Camassola ; Vanessa Schein ; F¨¢tima C.R. Guma ; Nance Beyer Nardi ; Vera Maria Treis Trindade
- 关键词：CNS ; Central Nervous System ; GAGs ; glycosaminoglycans ; HPTLC ; high performance thin-layer chromatography ; IDUA ; ¦Á-l-iduronidase ; KO ; Knockout ; MPS I ; Mucopolysaccharidosis I ; NANA ; N-acetyl-neuraminic acid ; Neu1 ; Neuraminidase 1 ; RT-sq-PCR ; Semi quantita
- 刊名：Gene
- 出版年：2013
- 出版时间：15 September, 2013
- 年：2013
- 卷：527
- 期：1
- 页码：109-114
- 全文大小：452 K
文摘
Mucopolysaccharidosis I (MPS I) is a congenital disorder caused by the deficiency of ¦Á-l-iduronidase (IDUA), with the accumulation of glycosaminoglycans (GAGs) in the CNS. Although GAG toxicity is not fully understood, previous works suggest a GAG-induced alteration in neuronal membrane composition. This study is aimed to evaluate the levels and distribution of gangliosides and cholesterol in different brain regions (cortex, cerebellum, hippocampus and hypothalamus) in a model using IDUA knockout (KO) mice (C57BL/6). Lipids were extracted with chloroform-methanol and then total gangliosides and cholesterol were determined, followed by ganglioside profile analyses. While no changes in cholesterol content were observed, the results showed a tissue dependent ganglioside alteration in KO mice: a total ganglioside increase in cortex and cerebellum, and a selective presence of GM3, GM2 and GD3 gangliosides in the hippocampus and hypothalamus. To elucidate this, we evaluated gene expression of ganglioside synthesis (GM3, GD3 and GM2/GD2 synthases) and degradation of (Neuraminidase1) enzymes in the cerebellum and hippocampus by RT-sq-PCR. The results obtained with KO mice showed a reduced expression of GD3 and GM2/GD2 synthases and Neuraminidase1 in cerebellum; and a decrease in GM2/GD2 synthase and Neuraminidase1 in the hippocampus. These data suggest that the observed ganglioside changes result from a combined effect of GAGs on ganglioside biosynthesis and degradation.