TY  - JOUR
A1  - Svirin, Evgeniy
A1  - Veniaminova, Ekaterina
A1  - Costa-Nunes, João Pedro
A1  - Gorlova, Anna
A1  - Umriukhin, Aleksei
A1  - Kalueff, Allan V.
A1  - Proshin, Andrey
A1  - Anthony, Daniel C.
A1  - Nedorubov, Andrey
A1  - Tse, Anna Chung Kwan
A1  - Walitza, Susanne
A1  - Lim, Lee Wei
A1  - Lesch, Klaus-Peter
A1  - Strekalova, Tatyana
T1  - Predation stress causes excessive aggression in female mice with partial genetic inactivation of tryptophan hydroxylase-2: evidence for altered myelination-related processes
JF  - Cells
N2  - The interaction between brain serotonin (5-HT) deficiency and environmental adversity may predispose females to excessive aggression. Specifically, complete inactivation of the gene encoding tryptophan hydroxylase-2 (Tph2) results in the absence of neuronal 5-HT synthesis and excessive aggressiveness in both male and female null mutant (Tph2\(^{−/−}\)) mice. In heterozygous male mice (Tph2\(^{+/−}\)), there is a moderate reduction in brain 5-HT levels, and when they are exposed to stress, they exhibit increased aggression. Here, we exposed female Tph2\(^{+/−}\) mice to a five-day rat predation stress paradigm and assessed their emotionality and social interaction/aggression-like behaviors. Tph2\(^{+/−}\) females exhibited excessive aggression and increased dominant behavior. Stressed mutants displayed altered gene expression of the 5-HT receptors Htr1a and Htr2a, glycogen synthase kinase-3 β (GSK-3β), and c-fos as well as myelination-related transcripts in the prefrontal cortex: myelin basic protein (Mbp), proteolipid protein 1 (Plp1), myelin-associated glycoprotein (Mag), and myelin oligodendrocyte glycoprotein (Mog). The expression of the plasticity markers synaptophysin (Syp) and cAMP response element binding protein (Creb), but not AMPA receptor subunit A2 (GluA2), were affected by genotype. Moreover, in a separate experiment, naïve female Tph2\(^{+/−}\) mice showed signs of enhanced stress resilience in the modified swim test with repeated swimming sessions. Taken together, the combination of a moderate reduction in brain 5-HT with environmental challenges results in behavioral changes in female mice that resemble the aggression-related behavior and resilience seen in stressed male mutants; additionally, the combination is comparable to the phenotype of null mutants lacking neuronal 5-HT. Changes in myelination-associated processes are suspected to underpin the molecular mechanisms leading to aggressive behavior.
KW  - tryptophan hydroxylase-2 (Tph2)
KW  - female aggression
KW  - 5-HT receptors
KW  - glycogen synthase kinase-3 β (GSK-3β)
KW  - myelination
KW  - predation stress
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267250
SN  - 2073-4409
VL  - 11
IS  - 6
ER  - 
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  -