TY - JOUR
T1 - Sex-Specific ADHD-like Behaviour, Altered Metabolic Functions, and Altered EEG Activity in Sialyltransferase ST3GAL5-Deficient Mice
AU - Strekalova, T.
AU - Veniaminova, E.
AU - Svirin, E.
AU - Kopeikina, E.
AU - Veremeyko, T.
AU - Yung, A.W.Y.
AU - Proshin, A.
AU - Tan, S.Z.K.
AU - Khairuddin, S.
AU - Lim, L.W.
AU - Lesch, K.P.
AU - Walitza, S.
AU - Anthony, D.C.
AU - Ponomarev, E.D.
N1 - Funding Information:
Funding: Research Grant Council, the Area of Excellence scheme from Hong Kong Government and SBS Incentive Scheme (2019–2020)—Bridging Fund (AoE/M-604/16 and SBS-BF(2019–2020)-01 to E.D.P.), Swiss-RF program-2020 (to T.S., S.W., and K.-P.L.), FSBSI “Institute of General Pathology and Pathophysiology” 0520-2019-0031 (to T.S and E.S) and the European Union’s Horizon 2020 (PhytoAPP, no. 10100764 to T.S. and D.C.A; Eat2beNICE, no. 728018 to T.S. and K.-P.L.).
Publisher Copyright:
© 2021 by the authors. Li-censee MDPI, Basel, Switzerland.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - lactosylceramide alpha-2
KW - 3-sialyltransferase (ST3GAL5)
KW - attention-deficit
KW - hyperactivity disorder (ADHD)
KW - insulin receptor (IR)
KW - sex differences
KW - electroencephalogram (EEG)
KW - mice
KW - GANGLIOSIDE GM3
KW - ANXIETY
KW - DISORDER
U2 - 10.3390/biom11121759
DO - 10.3390/biom11121759
M3 - Article
C2 - 34944404
SN - 2218-273X
VL - 11
JO - Biomolecules
JF - Biomolecules
IS - 12
M1 - 1759
ER -