Depression-resistant Phenotype in Mice Overexpressing Regulator of G Protein Signaling 8 (RGS8)

Kobayashi, Yuki; Takemoto, Risa; Yamato, Shogo; Okada, Tomoya; Iijima, Michihiko; Uematsu, Yoshikatsu; Chaki, Shigeyuki; Saito, Yumiko

doi:10.1016/j.neuroscience.2018.05.005

Cited by 16 publications

(6 citation statements)

References 53 publications

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“…Additionally, DisGeNET database analysis implicated hub genes in the development of depression and other diseases. Kobayashi reported that G protein signal transduction regulator 8 (RGS8) participated in the regulation of depressor-like behaviors by tuning ciliate MCHR1 expressed in the hippocampus CA1 region [ 30 ]. PaGenBase database analysis demonstrated that hub genes were mainly enriched in the lung, suggesting that the development of AS is potentially correlated with lung function.…”

Section: Discussionmentioning

confidence: 99%

Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data

Hao

Chen

et al. 2021

Aging

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While acknowledging carotid atherosclerosis (CAS) as a risk factor for ischemic stroke, reports on its pathogenesis are scarce. This study aimed to explore the potential mechanism of CAS through RNA-seq data analysis. Carotid intima tissue samples from CAS patients and healthy subjects were subjected to RNA-seq analysis, which yielded, 1,427 differentially expressed genes (DEGs) related to CAS. Further, enrichment analysis (Gene Ontology, KEGG pathway, and MOCDE analysis) was performed on the DEGs. Hub genes identified via the protein-protein interaction network (PPI) were then analyzed using TRRUST, DisGeNET, PaGenBase, and CMAP databases. Results implicated inflammation and immunity in the pathogenesis of CAS. Also, lung disease was associated with CAS. Hub genes were expressed in multiple diseases, mainly regulated by RELA and NFKB1. Moreover, three small-molecule compounds were found via the CMAP database for management of CAS; hub genes served as potential targets. Collectively, inflammation and immunity are the potential pathological mechanisms of CAS. This study implicates CeForanide, Chenodeoxycholic acid, and 0317956-0000 as potential drug candidates for CAS treatment.

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Section: Discussionmentioning

confidence: 99%

Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data

Hao

Chen

et al. 2021

Aging

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“…RGS8 is able to interact with the third intracellular loop of melanin-concentrating hormone (MCH) receptor 1 (MCHR1) and inhibits the calcium mobilization induced by melanin-concentrating hormone [ 94 ]. Increased RGS8 expression through the inhibition of the MCHR1 signaling in the hippocampal CA1 region may be related to the antidepressant-like behavior of RGS8 transgenic mice [ 95 ]. Although the expression of RGS8 protein has been reported in the hippocampal CA1 region, RGS8 knockout mice have normal brain development and no major abnormalities in other organs [ 95 , 96 ].…”

Section: The Role Of Recently Identified Dysregulated Moleculesmentioning

confidence: 99%

“…Increased RGS8 expression through the inhibition of the MCHR1 signaling in the hippocampal CA1 region may be related to the antidepressant-like behavior of RGS8 transgenic mice [ 95 ]. Although the expression of RGS8 protein has been reported in the hippocampal CA1 region, RGS8 knockout mice have normal brain development and no major abnormalities in other organs [ 95 , 96 ]. RGS8 protein is also expressed in testis, but RGS8 knockout mice are viable and fertile [ 96 ].…”

Section: The Role Of Recently Identified Dysregulated Moleculesmentioning

confidence: 99%

The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint

Kapfhammer

2022

IJMS

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Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominantly inherited progressive disorders with degeneration and dysfunction of the cerebellum. Although different subtypes of SCAs are classified according to the disease-associated causative genes, the clinical syndrome of the ataxia is shared, pointing towards a possible convergent pathogenic pathway among SCAs. In this review, we summarize the role of SCA-associated gene function during cerebellar Purkinje cell development and discuss the relationship between SCA pathogenesis and neurodevelopment. We will summarize recent studies on molecules involved in SCA pathogenesis and will focus on the mGluR1-PKCγ signaling pathway evaluating the possibility that this might be a common pathway which contributes to these diseases.

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“…Subsequent steps were performed in the same method as in Section 2.7. The brains of fasted mice were stained by the frozen section method (44,51). For AC3/MCHR1 staining in primary cilia, 8-μm sections were heated at 70°C for 20 min in Histo VT One for antigen retrieval and blocked with Blocking One Histo (Nacalai Tesque) for 5 min.…”

Section: Fasting Of Micementioning

confidence: 99%

Ciliary GPCR‐based transcriptome as a key regulator of cilia length control

et al. 2021

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The primary cilium is a plasma membrane-protruding sensory organelle that efficiently conveys signaling cascades in a highly ordered microenvironment. Its signaling is mediated, in part, by a limited set of GPCRs preferentially enriched in the cilium membrane. This includes melanin-concentrating hormone (MCH) receptor 1 (MCHR1), which plays a role in feeding and mood. In addition to its receptor composition, the length of the cilium is a characteristic parameter that is implicated in its function. We previously found that MCH can dynamically shorten cilia length via the Gi/o and Akt pathways in both MCHR1-expressing hTERT-RPE1 cells (hRPE1 cells) and rat hippocampal neurons. However, the detailed mechanisms by which MCH regulates cilia length through ciliary MCHR1 remains unclear. In this study, we aimed to determine the transcriptome changes in MCHR1-expressing hRPE1 cells in response to MCH to identify the target molecules involved in cilia length regulation via MCHR1 activation. RNA-sequencing analysis of ciliated cells subjected to MCH treatment showed upregulation of 424 genes and downregulation of 112 genes compared with static control cells. Validation by quantitative real-time PCR, knocking down, and CRISPR/Cas9-mediated knockout technology identified a molecule, PDZ and LIM domain-containing protein 5 (PDLIM5). Thus, it was considered as the most significant key factor for MCHR1-mediated shortening of cilia length. Additional analyses revealed that the actin-binding protein alpha-actinin 1/4 is a crucial downstream target of the PDLIM5 signaling pathway that exerts an effect on MCHR1-induced cilia shortening. In the endogenous MCHR1-expressing hippocampus, transcriptional upregulation of PDLIM5 and actinin 1/4, following the application of MCH, was detected when the MCHR1-positive cilia were shortened. Together, our transcriptome study based on ciliary MCHR1 function uncovered a novel and important regulatory step underlying cilia length control. These results will potentially serve as a basis for understanding the mechanism underlying the development of obesity and mood disorders.

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Depression-resistant Phenotype in Mice Overexpressing Regulator of G Protein Signaling 8 (RGS8)

Cited by 16 publications

References 53 publications

Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data

Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data

The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint

Ciliary GPCR‐based transcriptome as a key regulator of cilia length control

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