期刊
BIOMOLECULES
卷 11, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/biom11121759
关键词
lactosylceramide alpha-2; 3-sialyltransferase (ST3GAL5); attention-deficit; hyperactivity disorder (ADHD); insulin receptor (IR); sex differences; electroencephalogram (EEG); mice
资金
- Research Grant Council
- Hong Kong Government
- SBS Incentive Scheme (2019-2020)-Bridging Fund [AoE/M-604/16, SBS-BF(2019-2020)-01]
- Swiss-RF program-2020
- FSBSI Institute of General Pathology and Pathophysiology [0520-2019-0031]
- European Union [10100764, 728018]
Deficiency in GM3-derived gangliosides due to lack of ST3GAL5 enzyme can lead to severe neuropathology, including epilepsy and metabolic abnormalities. Knock-out mice lacking ST3Gal5 exhibit ADHD-like behaviors, altered metabolic measures, and EEG abnormalities, providing a useful platform for understanding the contribution of brain gangliosides to ADHD and associated comorbidities.
A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5(-/-)) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5(-/-) mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5(-/-) mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5(-/-) mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5(-/-) mice. Together, St3gal5(-/-) mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.
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