Silencing of RGS2 enhances hippocampal neuron regeneration and rescues depression-like behavioral impairments through activation of cAMP pathway

Zhu, Cheng; Li, Hui; Zheng, Ke; Liu, Linjing; Liu, Jiahong; Lv, Wei

doi:10.1016/j.brainres.2020.147018

Cited by 14 publications

(10 citation statements)

References 27 publications

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“…The copyright holder for this preprint this version posted February 8, 2023. ; https://doi.org/10.1101/2023.02.08.527622 doi: bioRxiv preprint Nevertheless, our results, revealing overrepresentation of immune-related GO terms among the downregulated genes in obese larvae, do not necessarily imply reduced inflammation, since among the genes validated by qRT-PCR (ptgs2a, nfkbiab, crema, rgs2 and nr4a1), most were able to suppress and/or induce inflammation depending on the conditions (Welty et al, 2016;Francés et al, 2015;Rodríguez-Calvo et al, 2017;Catrysse & van Loo, 2017;Cai & Liu, 2012;McNabb et al, 2020;Zhu et al, 2020). Moreover, the overrepresented immune system related GO terms among the downregulated genes in HFD-fed adult zebrafish belong to the telencephalon of the brain and not to the whole brain, adipose tissue or liver, which if analyzed instead, may have led to a very different conclusion.…”

Section: Discussionmentioning

confidence: 64%

“…Six of the 14 inflammation/immune-related DE transcripts were tested and successfully validated by qRT-PCR (Figure 2B). Most of these transcripts may suppress and/or induce inflammation, depending on the conditions (Welty et al , 2016; Francés et al , 2015; Rodríguez-Calvo et al , 2017; Catrysse & van Loo, 2017; Cai & Liu, 2012; McNabb et al , 2020; Zhu et al , 2020). The seemingly inverse roles of these regulators may hence be subject to additional control (e. g., via non-coding RNAs) under stress conditions.…”

Section: Resultsmentioning

confidence: 99%

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Inversely regulated immune-related processes mediate anxiety-obesity links in zebrafish

Yehuda

Madrer

Goldberg

et al. 2023

Preprint

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Anxiety disorders often associate with metabolic impairments, but the underlying developmental and molecular mechanisms are yet unknown. To seek RNAs that may link anxiety and obesity, we subjected RNA from zebrafish larvae of a caffeine-induced anxiety model and a high fat diet (HFD)-induced obesity model to RNA-sequencing. We found differentially expressed genes in the larval anxiety and obesity models, including long noncoding RNAs and transfer fragment RNAs. Surprisingly, they were inversely regulated and comprised overrepresentation of immune system pathways, e.g., interleukin signaling and inflammation. Similarly, inverse regulation persisted in adulthood, but with different overrepresented immune system processes, e.g., T cell activation, leukocyte cell-cell adhesion and antigen processing and presentation. Furthermore, unlike the known link in adult zebrafish, obesity in zebrafish larvae was not accompanied by anxiety-like behavior. These results may reflect an antagonistic pleiotropic phenomenon involving re-adjusted modulation of the anxiety-metabolic links with the immune system. Furthermore, the HFD potential to normalize the anxiety-upregulated immune-related genes may explain previously reported protective roles of high fat diet in rodent anxiety and Alzheimer's disease models.

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Section: Discussionmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Inversely regulated immune-related processes mediate anxiety-obesity links in zebrafish

Yehuda

Madrer

Goldberg

et al. 2023

Preprint

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“…cAMP signaling enhances the excitability of neural circuits and has a facilitative effect on memory. Activation of the cAMP pathway enhances hippocampal neuron regeneration in mice with a depressive-like behavior [ 60 ]. The PI3K/Akt signaling pathway is the main signaling pathway through which central neuroprotective agents act, and it is one of the more maturely studied pathways.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Mechanism of Action of Trachelospermi Caulis et Folium for Depression Based on Experiments: Combining Network Pharmacology and Molecular Docking

Wen

Fan

Xiong

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To reveal the safety, efficacy, and mechanism of action of Trachelospermi Caulis et Folium (TCEF) for treating depression. Methods. The maximum dose method was employed to evaluate the safety of TCEF, and its antidepressant activity was assessed using the tail suspension and sugar water depletion tests. The main components of TCEF were determined using ultrahigh performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometer (UHPLC-Q-EOMS). The active ingredients and their action targets were obtained using network pharmacology with SwissADME and SwissTargetPrediction screening, and the targets of depression were obtained using GeneCards, DrugBank, etc. The drug and depression-related targets were intersected and analyzed via PPI network, GO, and KEGG. Subsequently, the binding ability of the core components of TCEF to the core targets was validated via molecular docking and simulation. Results. No statistically significant difference was observed between the normal and TCEF groups in terms of body weight, visceral index, and biochemical parameters ( P > 0.05 ). Compared with the model group, all dose groups of TCEF had reduced the immobility time of tail suspension ( P < 0.05 ) and increased the rate of sugar water consumption ( P < 0.05 ). UHPLC-Q-EOMS was employed to identify 59 major components of TCEF, and network pharmacology analysis was used to screen 48 active components of TCEF for treating depression, corresponding to 139 relevant targets, including ALB, AKT1, TNF, ESR1, and CTNNB1. The involved pathways include neuroactive ligand-receptor interaction. The molecular docking results indicated that the core components have a good binding activity to the core targets. Conclusions. TCEF is a relatively safe antidepressant medicine that exerts therapeutic effects through multiple components, targets, and pathways, providing a new idea and theoretical basis for future use of TCEF to treat depression.

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“…GPR40, also called free fatty acid receptor 1 (FFAR1), is a G protein-coupled receptor (GPCR) activated by long-chain fatty acids, such as PA [31]. Activation of GPR40 receptor with cognate ligands elevates intracellular Ca 2+ levels and increase PKC activity via coupling to Gα q/11 [31][32][33], a pathway associated with RGS2 up-regulation [34][35][36]. Consistently with the idea that GPR40 may mediate the observed effects of PA on RGS2 expression, Hernandez-Caceres, et al [32] recently demonstrated that PA reduces insulin sensitivity through GPR40 activation in hypothalamic neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes

et al. 2021

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Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.

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Silencing of RGS2 enhances hippocampal neuron regeneration and rescues depression-like behavioral impairments through activation of cAMP pathway

Cited by 14 publications

References 27 publications

Inversely regulated immune-related processes mediate anxiety-obesity links in zebrafish

Inversely regulated immune-related processes mediate anxiety-obesity links in zebrafish

Exploring the Mechanism of Action of Trachelospermi Caulis et Folium for Depression Based on Experiments: Combining Network Pharmacology and Molecular Docking

The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes

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