Sex-Specific ADHD-like Behaviour, Altered Metabolic Functions, and Altered EEG Activity in Sialyltransferase ST3GAL5-Deficient Mice

Biomolecules

Susanne Walitza¹  Tatyana Strekalova²  Evgeniy Svirin²  Klaus-Peter Lesch²  Andrey Proshin³  Daniel C. Anthony⁴  Ekaterina Veniaminova⁴  Ekaterina Kopeikina⁵  Tatyana Veremeyko⁵  Eugene D. Ponomarev⁵  Amanda W. Y. Yung⁵  Lee Wei Lim⁶  Sharafuddin Khairuddin⁶  Shawn Zheng Kai Tan⁶ 

[1] Department for Child and Adolescent Psychiatry and Psychotherapy of the University of Zürich and the Zürich University Hospital of Psychiatry, 8070 Zürich, Switzerland;Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, 6229 ER Maastricht, The Netherlands;Laboratory of General Physiology of Functional Systems, Federal State Budgetary Scientific Institution, P.K. Anokhin Research Institute of Normal Physiology, 125315 Moscow, Russia;Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia;School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China;School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;

关键词: lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5);    attention-deficit/hyperactivity disorder (ADHD);    insulin receptor (IR);    sex differences;    electroencephalogram (EEG);    mice;   

DOI  :  10.3390/biom11121759

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown