Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, 6229 ER Maastricht, The Netherlands.
Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
Biomolecules. 2021 Nov 24;11(12):1759. doi: 10.3390/biom11121759.
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 () 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 mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. 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 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 mice. Together, 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.
GM3 衍生神经节苷脂缺乏症是由于缺乏乳糖基神经酰胺-α-2,3-唾液酸转移酶（ST3GAL5）引起的，可导致严重的神经病理学改变，包括癫痫发作和代谢异常。这种酶对神经节苷脂生成的破坏也可能在神经精神疾病的发展中起作用。ST3Gal5 敲除（）小鼠缺乏 a-、b-和 c-系列神经节苷脂，但没有明显的神经病理学表现，这可能是由于产生了代偿性 0 系列糖脂。在这里，我们试图研究是否可能存在注意力缺陷多动障碍（ADHD）样行为。此外，我们还评估了潜在的代谢和脑电图（EEG）异常。对 小鼠进行了行为测试、葡萄糖耐量测试，并测量了大脑和外周 A 和 B 胰岛素受体（IR）同工型的表达水平。我们发现 小鼠表现出运动过度活跃、冲动、恐惧新事物和焦虑样行为。该基因型还改变了血糖水平和葡萄糖耐量。性别偏倚与体重和外周 IR 表达一致。EEG 分析显示 小鼠的振幅增加。总之， 小鼠表现出 ADHD 样行为、代谢和 EEG 改变，为更好地理解大脑神经节苷脂对 ADHD 及相关共病的贡献提供了有用的平台。
