TY  - JOUR
A1  - Gorlova, Anna
A1  - Svirin, Evgeniy
A1  - Pavlov, Dmitrii
A1  - Cespuglio, Raymond
A1  - Proshin, Andrey
A1  - Schroeter, Careen A.
A1  - Lesch, Klaus-Peter
A1  - Strekalova, Tatyana
T1  - Understanding the role of oxidative stress, neuroinflammation and abnormal myelination in excessive aggression associated with depression: recent input from mechanistic studies
JF  - International Journal of Molecular Sciences
N2  - Aggression and deficient cognitive control problems are widespread in psychiatric disorders, including major depressive disorder (MDD). These abnormalities are known to contribute significantly to the accompanying functional impairment and the global burden of disease. Progress in the development of targeted treatments of excessive aggression and accompanying symptoms has been limited, and there exists a major unmet need to develop more efficacious treatments for depressed patients. Due to the complex nature and the clinical heterogeneity of MDD and the lack of precise knowledge regarding its pathophysiology, effective management is challenging. Nonetheless, the aetiology and pathophysiology of MDD has been the subject of extensive research and there is a vast body of the latest literature that points to new mechanisms for this disorder. Here, we overview the key mechanisms, which include neuroinflammation, oxidative stress, insulin receptor signalling and abnormal myelination. We discuss the hypotheses that have been proposed to unify these processes, as many of these pathways are integrated for the neurobiology of MDD. We also describe the current translational approaches in modelling depression, including the recent advances in stress models of MDD, and emerging novel therapies, including novel approaches to management of excessive aggression, such as anti-diabetic drugs, antioxidant treatment and herbal compositions.
KW  - major depressive disorder (MDD)
KW  - aggression
KW  - neuroinflammation
KW  - oxidative stress
KW  - insulin receptor
KW  - myelination
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304917
SN  - 1422-0067
VL  - 24
IS  - 2
ER  - 
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  -