Sex-specific ADHD-like behaviour, altered metabolic functions, and altered EEG activity in sialyltransferase ST3GAL5-deficient mice

Please always quote using this URN: urn:nbn:de:bvb:20-opus-250071
  • 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 toA 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.show moreshow less

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Author: Tatyana Strekalova, Ekaterina Veniaminova, Evgeniy Svirin, Ekaterina Kopeikina, Tatyana Veremeyko, Amanda W. Y. Yung, Andrey Proshin, Shawn Zheng Kai Tan, Sharafuddin Khairuddin, Lee Wei Lim, Klaus-Peter Lesch, Susanne Walitza, Daniel C. Anthony, Eugene D. Ponomarev
URN:urn:nbn:de:bvb:20-opus-250071
Document Type:Journal article
Faculties:Medizinische Fakultät / Lehrstuhl für Molekulare Psychiatrie
Language:English
Parent Title (English):Biomolecules
ISSN:2218-273X
Year of Completion:2021
Volume:11
Issue:12
Article Number:1759
Source:Biomolecules (2021) 11:12, 1759. https://doi.org/10.3390/biom11121759
DOI:https://doi.org/10.3390/biom11121759
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:attention-deficit/hyperactivity disorder (ADHD); electroencephalogram (EEG); insulin receptor (IR); lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5); mice; sex differences
Release Date:2023/05/26
Date of first Publication:2021/11/24
EU-Project number / Contract (GA) number:10100764
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International