TY - JOUR
T1 - Sex-specific adhd-like behaviour, altered metabolic functions and altered eeg activity in sialyltransferase st3gal5-deficient mice
AU - Strekalova, Tatyana
AU - Veniaminova, Ekaterina
AU - Svirin, Evgeniy
AU - Kopeikina, Ekaterina
AU - Veremeyko, Tatyana
AU - Yung, Amanda W.Y.
AU - Proshin, Andrey
AU - Tan, Shawn Zheng Kai
AU - Khairuddin, Sharafuddin
AU - Lim, Lee Wei
AU - Lesch, Klaus Peter
AU - Walitza, Susanne
AU - Anthony, Daniel C.
AU - Ponomarev, Eugene D.
N1 - Publisher Copyright:
© 2021 by the authors. Li-censee MDPI, Basel, Switzerland.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Attention-deficit/hyperactivity disorder (ADHD)
KW - Electroencephalogram (EEG)
KW - Insulin receptor (IR)
KW - Lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)
KW - Mice
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85119653559&partnerID=8YFLogxK
U2 - 10.3390/biom11121759
DO - 10.3390/biom11121759
M3 - Article
C2 - 34944404
AN - SCOPUS:85119653559
SN - 2218-273X
VL - 11
JO - Biomolecules
JF - Biomolecules
IS - 12
M1 - 1759
ER -