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  - Gorlova, Anna
A1  - Pavlov, Dmitrii
A1  - Anthony, Daniel C.
A1  - Ponomarev, Eugene D.
A1  - Sambon, Margaux
A1  - Proshin, Andrey
A1  - Shafarevich, Igor
A1  - Babaevskaya, Diana
A1  - Lesch, Klaus-Peter
A1  - Bettendorff, Lucien
A1  - Strekalova, Tatyana
T1  - Thiamine and benfotiamine counteract ultrasound-induced aggression, normalize AMPA receptor expression and plasticity markers, and reduce oxidative stress in mice
JF  - Neuropharmacology
N2  - The negative societal impacts associated with the increasing prevalence of violence and aggression is increasing, and, with this rise, is the need to understand the molecular and cellular changes that underpin ultrasound-induced aggressive behavior. In mice, stress-induced aggression is known to alter AMPA receptor subunit expression, plasticity markers, and oxidative stress within the brain. Here, we induced aggression in BALB/c mice using chronic ultrasound exposure and examined the impact of the psychoactive anti-oxidant compounds thiamine (vitamin B1), and its derivative benfotiamine, on AMPA receptor subunit expression, established plasticity markers, and oxidative stress. The administration of thiamine or benfotiamine (200 mg/kg/day) in drinking water decreased aggressive behavior following 3-weeks of ultrasound exposure and benfotiamine, reduced floating behavior in the swim test. The vehicle-treated ultrasound-exposed mice exhibited increases in protein carbonyl and total glutathione, altered AMPA receptor subunits expression, and decreased expression of plasticity markers. These ultrasound-induced effects were ameliorated by thiamine and benfotiamine treatment; in particular both antioxidants were able to reverse ultrasound-induced changes in GluA1 and GluA2 subunit expression, and, within the prefrontal cortex, significantly reversed the changes in protein carbonyl and polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression levels. Benfotiamine was usually more efficacious than thiamine. Thus, the thiamine compounds were able to counteract ultrasound-induced aggression, which was accompanied by the normalization of markers that have been showed to be associated with ultrasound-induced aggression. These commonly used, orally-active compounds may have considerable potential for use in the control of aggression within the community.

This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.
KW  - aggression
KW  - emotional stress
KW  - brain oxidative stress
KW  - plasticity
KW  - thiamine
KW  - mice
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227439
VL  - 156
ER  -