期刊
BIOMOLECULES
卷 11, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/biom11010007
关键词
Krabbe disease; Twitcher mouse; psychosine; visual system; visual cortex; astrogliosis
资金
- European Leukodystrophy Association (ELA) International [ELA 2019-008I2, ELA 2018-008F2]
This study provides a comprehensive characterization of morphological and functional alterations in the visual system of Twitcher (TWI) mouse model of Krabbe disease. The findings demonstrate defective basic functional properties in the primary visual cortex, along with specific neuropathological alterations and increasing PSY accumulation over time in the brain and optic nerves.
Krabbe disease (KD, or globoid cell leukodystrophy; OMIM #245200) is an inherited neurodegenerative condition belonging to the class of the lysosomal storage disorders. It is caused by genetic alterations in the gene encoding for the enzyme galactosylceramidase, which is responsible for cleaving the glycosydic linkage of galatosylsphingosine (psychosine or PSY), a highly cytotoxic molecule. Here, we describe morphological and functional alterations in the visual system of the Twitcher (TWI) mouse, the most used animal model of Krabbe disease. We report in vivo electrophysiological recordings showing defective basic functional properties of the TWI primary visual cortex. In particular, we demonstrate a reduced visual acuity and contrast sensitivity, and a delayed visual response. Specific neuropathological alterations are present in the TWI visual cortex, with reduced myelination, increased astrogliosis and microglia activation, and around the whole brain. Finally, we quantify PSY content in the brain and optic nerves by high-pressure liquid chromatography-mass spectrometry methods. An increasing PSY accumulation with time, the characteristic hallmark of KD, is found in both districts. These results represent the first complete characterization of the TWI visual system. Our data set a baseline for an easy testing of potential therapies for this district, which is also dramatically affected in KD patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据