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  - Veniaminova, Ekaterina
A1  - Cespuglio, Raymond
A1  - Cheung, Chi Wai
A1  - Umriukhin, Alexei
A1  - Markova, Nataliia
A1  - Shevtsova, Elena
A1  - Lesch, Klaus-Peter
A1  - Anthony, Daniel C.
A1  - Strekalova, Tatyana
T1  - Autism-like behaviours and memory deficits result from a Western Diet in mice
JF  - Neural Plasticity
N2  - Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.
KW  - diet
KW  - autism-like behavior
KW  - mice
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158211
ER  -