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.…
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 |
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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): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |