Sex-specific adhd-like behaviour, altered metabolic functions and altered eeg activity in sialyltransferase st3gal5-deficient mice

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-al-pha-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 behaviour. 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 be-haviours, altered metabolic and EEG measures providing a useful platform for better understand-ing of the contribution of brain gangliosides to ADHD and associated comorbidities.

Original languageEnglish
Article number1759
JournalBiomolecules
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

Keywords

  • Attention-deficit/hyperactivity disorder (ADHD)
  • Electroencephalogram (EEG)
  • Insulin receptor (IR)
  • Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)
  • Mice
  • Sex differences

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