PKBβ/AKT2 deficiency impacts brain mTOR signaling, prefrontal cortical physiology, hippocampal plasticity and select murine behaviors

Palumbo, Sara; Paterson, Clare; Yang, Feng; Hood, Veronica; Law, Amanda J.

doi:10.1038/s41380-020-00964-4

Cited by 22 publications

(19 citation statements)

References 75 publications

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“…Recent research on an isoform of serine/threonine protein kinase (v-AKT) AKT-2 supports this observation. In AKT -2 gene knock out mice, low AKT-2 levels correlated with the impairment of long-term potentiation (LTP) and electrophysiological properties of neurons causing hippocampal circuit disfunction [ 60 ]. The expression of AKT-2 is low in patients with bipolar disorder and may be linked to electrophysiological disfunctions observed in patients with this diagnosis [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review

Wilkowska

Wiglusz

Jakuszkowiak-Wojten

et al. 2022

Cells

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Background and Objectives: Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented. Materials and Methods: PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied. Results: Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms. Conclusions: The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine’s side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine–lamotrigine combination in bipolar patients.

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Section: Discussionmentioning

confidence: 99%

Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review

Wilkowska

Wiglusz

Jakuszkowiak-Wojten

et al. 2022

Cells

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“…According to the degree value and the betweenness centrality, PPI analysis network topology analysis screened AKT1 and IL-6, and 42 core targets, such as IL1B, CASP3, and MAPK3, were mainly related to immunity, in ammation, oxidative stress, and neovascularization. AKT1 is involved in the regulation of processes such as metabolism, proliferation, growth and angiogenesis [49]. IL-6 is one of the most biologically active cytokines and can be called a sleepy mediator.…”

Section: Discussionmentioning

confidence: 99%

To Explore the Network Pharmacology and Molecular Docking Mechanism of Chaihu Shugan Powder with the “Same Treatment for Different Diseases” for Insomnia and Depression Based on the COVID-19 Pandemic

Wang

Chen

et al. 2022

Preprint

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Background: The classic prescription Chaihu Shugan Powder (CHSGP) has been widely used in clinical Chinese medicine treatment and has clear clinical effects in the treatment of emotional diseases. Based on the increasing incidence of emotional diseases such as insomnia and depression in the population during the COVID-19 pandemic, we will explore the mechanism of CHSGP in the treatment of insomnia and depression with “Same Treatment for Different Diseases”. Methods: Using a bioinformatics and network pharmacology platform, protein database and STRING database, we collected CHSGP chemical composition and related target data and constructed a "component-target" action network through Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis. Molecular docking technology was used to verify key active ingredients and core targets. Results: A total of 119 active compounds of CHSGP were screened, such as quercetin, kaempferol, and β-sitosterol, and 113 common related targets overlapped with insomnia and depression. GO enrichment and KEGG pathway analysis mainly involved immune, inflammation, cell proliferation, apoptosis, endocrine and other related targets and signaling pathways. Molecular docking showed that small molecular compounds (kaempferol, luteolin, quercetin, 7-methoxy-2-methyl isoflavone and beta-sitosterol) had good binding effects with five target proteins (AKT1, IL1B, IL-6, FOS, GSK3B) to play a role in regulating immunity, the inflammatory response, cell proliferation, apoptosis, and endocrine signaling. Conclusions: Under the context of the COVID-19 pandemic, it revealed the complex mechanism of multicomponent, multitarget, and multipathway of the classic CHSGP for insomnia and depression, laying a theoretical foundation for its clinical application of its "same treatment for different diseases".

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“…These KEGG pathways interact with each other and participate in the ECM-receptor interaction pathway ( Kerrisk et al 2014 , Mardpour et al 2019 , Sun et al 2020 , Virtuoso et al 2020 , Su et al 2021 ). Furthermore, PI3K/AKT signalling pathway is strongly associated with anxiety and depression behaviours through hippocampal plasticity, cell growth, proliferation, survival, and metabolism ( Gimenez-Llort et al 2020 , Neis et al 2020 , Palumbo et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception

et al. 2021

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The number of children born after assisted reproductive technology (ART) are accumulating rapidly and the healthy problems of the children are extensively concerned. This study aims to evaluate whether the ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET) and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Aged (18 months old), but not young (3 months old) male offspring, in the IVF-ET and IVF-FET groups, compared with these in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA Sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in future.

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PKBβ/AKT2 deficiency impacts brain mTOR signaling, prefrontal cortical physiology, hippocampal plasticity and select murine behaviors

Cited by 22 publications

References 75 publications

Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review

Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review

To Explore the Network Pharmacology and Molecular Docking Mechanism of Chaihu Shugan Powder with the “Same Treatment for Different Diseases” for Insomnia and Depression Based on the COVID-19 Pandemic

Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception

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