Stress-induced aggression in heterozygous TPH2 mutant mice is associated with alterations in serotonin turnover and expression of 5-HT6 and AMPA subunit 2A receptors

Gorlova, Anna; Ortega, Guillermo J.; Waider, Jonas; Bazhenova, Natalia; Veniaminova, Ekaterina; Proshin, A. T.; Kalueff, Allan V.; Anthony, Daniel C.; Lesch, Klaus‐Peter; Strekalova, Tatyana

doi:10.1016/j.jad.2020.04.014

Cited by 21 publications

(35 citation statements)

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“…Regions such as the cingulate cortex, ventromedial, and the orbitofrontal PFC were shown to have reduced serotonergic activity during impulsive aggression (Siever et al, 1999 ). Similar findings also reproduced in non-human animal models (Harrison et al, 1997 ; Kästner et al, 2019 ; Gorlova et al, 2020 ).…”

Section: Serotonin In Aud and Aggressionsupporting

confidence: 64%

Alcohol, Aggression, and Violence: From Public Health to Neuroscience

et al. 2021

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Alcohol has been associated with violent crimes and domestic violence across many nations. Various etiological factors were linked to chronic alcohol use and violence including psychiatric comorbidities of perpetrators such as personality disorders, mood disorders, and intermittent explosive disorders. Aggression is the precursor of violence and individuals prone to aggressive behaviors are more likely to commit impulsive violent crimes, especially under the influence of alcohol. Findings from brain studies indicate long-term alcohol consumption induced morphological changes in brain regions involved in self-control, decision-making, and emotional processing. In line with this, the inherent dopaminergic and serotonergic anomalies seen in aggressive individuals increase their susceptibility to commit violent crimes when alcohol present in their system. In relation to this, this article intends to investigate the influence of alcohol on aggression with sociopsychological and neuroscientific perspectives by looking into comorbidity of personality or mood disorders, state of the mind during alcohol consumption, types of beverages, environmental trigger, neurochemical changes, and gender differences that influence individual responses to alcohol intake and susceptibility to intoxicated aggression.

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Section: Serotonin In Aud and Aggressionsupporting

confidence: 64%

Alcohol, Aggression, and Violence: From Public Health to Neuroscience

et al. 2021

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“…Thus, for Htr1a, the sex-dependent behavioral effects that has been reported after the pharmacological -148 -targeting of Htr1a in rodents [43] suggests that there is likely to be a differential role for this receptor in abnormal aggression in males and females. Moreover, lowered gene expression of Htr6 reported in stressed male Tph2 +/− mice [21] was also found in stressed female mutants in the present study.…”

Section: Discussionsupporting

confidence: 85%

“…he relevance of gene × environment interaction in the manifestation of pathological aggression is further supported by studies in male mice heterozygous for Tph2 gene inactivation, which exhibit a moderate brain 5-HT reduction of 15-20% [7,8]. Tph2 +/− mice showed -137 -unaltered social behavior at baseline, but after subchronic rat exposure stress demonstrated markedly increased levels of aggression and dominancy, and reduced sociability compared to wild type controls [20,21]. These changes were accompanied by profound alterations in the brain metabolism of 5-HT, dopamine, and norepinephrine.…”

Section: Introductionmentioning

confidence: 97%

“…We adopted a previously validated fiveday rat exposure paradigm with includes an element of restraint, by virtue of limiting the extent free movement available to the Tph2 +/− female mice. This approach has been shown to induce changes in monoamine transmitters, neurogenesis, oxidative stress [24,25], as well as aggressive behavior in male Tph2 +/− mice [20,21]. The rat exposure -138 -procedure applied here has been shown to result in increases in blood levels of CORT in C57BL/6 mice at 6 and 24 h post-stress [25].…”

Section: Introductionmentioning

confidence: 99%

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Excessive aggression, ADHD- and ASD-like phenotypes in TPH2- and brain ganglioside-deficient mice

Svirin¹

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“…The total protein concentration was adjusted to 1-10 mg/ml with 1 × sample diluent, and protein carbonyls were determined according to the guidelines of the manufacturer using the GloMax Multi Detection System (Promega, Madison, WI, USA) equipped with a fluorescence module (485/540 nm filter set). Results were normalized to protein concentration as described previously (55,65).…”

Section: Protein Carbonyl Assaymentioning

confidence: 99%

Increased Oxidative Stress in the Prefrontal Cortex as a Shared Feature of Depressive- and PTSD-Like Syndromes: Effects of a Standardized Herbal Antioxidant

et al. 2021

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Major depression (MD) and posttraumatic stress disorder (PTSD) share common brain mechanisms and treatment strategies. Nowadays, the dramatically developing COVID-19 situation unavoidably results in stress, psychological trauma, and high incidence of MD and PTSD. Hence, the importance of the development of new treatments for these disorders cannot be overstated. Herbal medicine appears to be an effective and safe treatment with fewer side effects than classic pharmaca and that is affordable in low-income countries. Currently, oxidative stress and neuroinflammation attract increasing attention as important mechanisms of MD and PTSD. We investigated the effects of a standardized herbal cocktail (SHC), an extract of clove, bell pepper, basil, pomegranate, nettle, and other plants, that was designed as an antioxidant treatment in mouse models of MD and PTSD. In the MD model of “emotional” ultrasound stress (US), mice were subjected to ultrasound frequencies of 16–20 kHz, mimicking rodent sounds of anxiety/despair and “neutral” frequencies of 25–45 kHz, for three weeks and concomitantly treated with SHC. US-exposed mice showed elevated concentrations of oxidative stress markers malondialdehyde and protein carbonyl, increased gene and protein expression of pro-inflammatory cytokines interleukin (IL)-1β and IL-6 and other molecular changes in the prefrontal cortex as well as weight loss, helplessness, anxiety-like behavior, and neophobia that were ameliorated by the SHC treatment. In the PTSD model of the modified forced swim test (modFST), in which a 2-day swim is followed by an additional swim on day 5, mice were pretreated with SHC for 16 days. Increases in the floating behavior and oxidative stress markers malondialdehyde and protein carbonyl in the prefrontal cortex of modFST-mice were prevented by the administration of SHC. Chromatography mass spectrometry revealed bioactive constituents of SHC, including D-ribofuranose, beta-D-lactose, malic, glyceric, and citric acids that can modulate oxidative stress, immunity, and gut and microbiome functions and, thus, are likely to be active antistress elements underlying the beneficial effects of SHC. Significant correlations of malondialdehyde concentration in the prefrontal cortex with altered measures of behavioral despair and anxiety-like behavior suggest that the accumulation of oxidative stress markers are a common biological feature of MD and PTSD that can be equally effectively targeted therapeutically with antioxidant therapy, such as the SHC investigated here.

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Stress-induced aggression in heterozygous TPH2 mutant mice is associated with alterations in serotonin turnover and expression of 5-HT6 and AMPA subunit 2A receptors

Cited by 21 publications

References 57 publications

Alcohol, Aggression, and Violence: From Public Health to Neuroscience

Alcohol, Aggression, and Violence: From Public Health to Neuroscience

Excessive aggression, ADHD- and ASD-like phenotypes in TPH2- and brain ganglioside-deficient mice

Increased Oxidative Stress in the Prefrontal Cortex as a Shared Feature of Depressive- and PTSD-Like Syndromes: Effects of a Standardized Herbal Antioxidant

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