TY  - JOUR
A1  - Strekalova, Tatyana
A1  - Veniaminova, Ekaterina
A1  - Svirin, Evgeniy
A1  - Kopeikina, Ekaterina
A1  - Veremeyko, Tatyana
A1  - Yung, Amanda W. Y.
A1  - Proshin, Andrey
A1  - Tan, Shawn Zheng Kai
A1  - Khairuddin, Sharafuddin
A1  - Lim, Lee Wei
A1  - Lesch, Klaus-Peter
A1  - Walitza, Susanne
A1  - Anthony, Daniel C.
A1  - Ponomarev, Eugene D.
T1  - Sex-specific ADHD-like behaviour, altered metabolic functions, and altered EEG activity in sialyltransferase ST3GAL5-deficient mice
JF  - Biomolecules
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.
KW  - lactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)
KW  - attention-deficit/hyperactivity disorder (ADHD)
KW  - insulin receptor (IR)
KW  - sex differences
KW  - electroencephalogram (EEG)
KW  - mice
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250071
SN  - 2218-273X
VL  - 11
IS  - 12
ER  - 
TY  - JOUR
A1  - Rivero, Olga
A1  - Alhama-Riba, Judit
A1  - Ku, Hsing-Ping
A1  - Fischer, Matthias
A1  - Ortega, Gabriela
A1  - Álmos, Péter
A1  - Diouf, David
A1  - van den Hove, Daniel
A1  - Lesch, Klaus-Peter
T1  - Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation
JF  - Frontiers in Genetics
N2  - Genome wide association meta-analysis identified ST3GAL3, a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in ST3GAL3 are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of ST3GAL3 haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since St3gal3 null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of St3gal3 in heterozygous (HET) knockout (St3gal3±) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways. Our results reveal that male St3gal3 HET mice display cognitive deficits, while female HET animals show increased activity, as well as increased cognitive control, compared to their wildtype littermates. In addition, we observed subtle alterations in the expression of several markers implicated in oligodendrogenesis, myelin formation, and protein sialylation as well as cell adhesion/synaptic target glycoproteins of ST3GAL3 in a brain region- and/or sex-specific manner. Taken together, our findings indicate that haploinsufficiency of ST3GAL3 results in a sex-dependent alteration of cognition, behavior and markers of brain plasticity.
KW  - sialyltransferase
KW  - sialic acid
KW  - psychiatric disorders
KW  - attention-deficit/hyperactivity disorder (ADHD)
KW  - prefrontal cortex
KW  - hippocampus
KW  - mouse model
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246855
SN  - 1664-8021
VL  - 12
ER  -