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

T. Strekalova, E. Veniaminova, E. Svirin, E. Kopeikina, T. Veremeyko, A.W.Y. Yung, A. Proshin, S.Z.K. Tan, S. Khairuddin, L.W. Lim, K.P. Lesch, S. Walitza, D.C. Anthony, E.D. Ponomarev*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)


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.
Original languageEnglish
Article number1759
Number of pages9
Issue number12
Publication statusPublished - 1 Dec 2021


  • lactosylceramide alpha-2
  • 3-sialyltransferase (ST3GAL5)
  • attention-deficit
  • hyperactivity disorder (ADHD)
  • insulin receptor (IR)
  • sex differences
  • electroencephalogram (EEG)
  • mice

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