Role of Rph3A in brain injury induced by experimental cerebral ischemia‐reperfusion model in rats

Zhu, Xianlong; Li, Haiying; You, Wanchun; Yu, Zhengquan; Wang, Zongqi; Shen, Haitao; Li, Xiang; Yu, Hao; Wang, Zhong; Chen, Gang

doi:10.1111/cns.13850

Cited by 14 publications

(5 citation statements)

References 51 publications

(88 reference statements)

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“…Interestingly, a recent study has demonstrated that RPH3A overexpression improves motor behavior in the PD mice model, and is a novel molecular target to counteract α-syn-induced synaptic failure (49). Besides, a study has suggested that the increase in Rph3A in the brain penumbra may be an endogenous protective mechanism against ischemia-reperfusion injury, which is mainly dominated by astrocytes (50). RPH3A loss correlated with dementia severity, cholinergic deafferentation, and increased β-amyloid (Aβ) concentrations (51).…”

Section: Discussionmentioning

confidence: 99%

Identification and Experimental Validation of Parkinson’s Disease with Major Depressive Disorder Common Genes

et al. 2023

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Parkinson's disease (PD) is the second most common neurodegenerative disease that affects about 10 million people worldwide. Non-motor and motor symptoms usually accompany PD. Major depressive disorder (MDD) is one of the non-motor manifestations of PD it remains unrecognized and undertreated effectively. MDD in PD has complicated pathophysiologies and remains unclear. The study aimed to explore the candidate genes and molecular mechanisms of PD with MDD. PD (GSE6613) and MDD (GSE98793) gene expression pro les were downloaded from Gene Expression Omnibus (GEO). Above all, the data of the two datasets were standardized separately, and differentially expressed genes (DEGs) were obtained by using the Limma package of R. Take the intersection of the two differential genes and remove the genes with inconsistent expression trends. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were investigated to explore the function of the common DEGs. Additionally, the construction of the protein-protein interaction (PPI) network was to search the hub genes, and then the least absolute shrinkage and selection operator (LASSO) regression was used to further identify the key genes. GSE99039 for PD and GSE201332 for MDD were performed to validate the hub genes by the violin plot and receiver operating characteristic (ROC) curve. Last but not least, immune cell dysregulation in PD was investigated by immune cell in ltration. As a result, a total of 45 common genes with the same trend. Functional analysis revealed that they were enriched in neutrophil degranulation, secretory granule membrane, and leukocyte activation. LASSO was performed on 8 candidate hub genes after CytoHubba ltered 14 node genes. Finally, AQP9, SPI1, and RPH3A were validated by GSE99039 and GSE201332. Additionally, the three genes were also detected by the qPCR in vivo model with the same phenomenon. The co-occurrence of PD and MDD can be attributed to AQP9, SPI1, and RPH3A genes. Neutrophils and monocytes in ltration play important roles in the development of PD and MDD. Novel insights may be gained from the ndings for the study of mechanisms.

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Section: Discussionmentioning

confidence: 99%

Identification and Experimental Validation of Parkinson’s Disease with Major Depressive Disorder Common Genes

et al. 2023

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“…S100a8 and S100a9 upregulation is representative of a pro-inflammatory state in injured peripheral nerves and induces microglia activation [ 17 , 80 ]. Finally, several genes related to neuronal function are downregulated in P1.hMR mice, such as genes encoding for rabphilin 3a ( Rph3a ), secretogranin ( Scg2 ) and Kinesin Family Member 5A ( Kif5a ), respectively, important for synaptic transmission [ 67 , 71 , 87 ], abundantly expressed by trigeminal neurons innervating the eye [ 63 , 64 ] and a crucial regulator of neurodegeneration [ 65 ]. Whilst an important proportion of neuronal RNA is missing due to the lack of neuronal bodies in the rodent choroid, the regulated genes/pathways reflect potential underlying mechanisms linking chorioretinopathy with choroidal neuropathy.…”

Section: Discussionmentioning

confidence: 99%

The choroidal nervous system: a link between mineralocorticoid receptor and pachychoroid

Leclercq,

Weiner,

Zola

et al. 2023

Acta Neuropathol

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Central serous chorioretinopathy (CSCR) belongs to the pachychoroid spectrum, a pathological phenotype of the choroidal vasculature, in which blood flow is under the choroidal nervous system (ChNS) regulation. The pathogenesis of CSCR is multifactorial, with the most recognised risk factor being intake of glucocorticoids, which activate both the gluco- and the mineralocorticoid (MR) receptors. As MR over-activation is pathogenic in the retina and choroid, it could mediate the pathogenic effects of glucocorticoids in CSCR. But the role of MR signalling in pachychoroid is unknown and whether it affects the ChNS has not been explored. Using anatomo-neurochemical characterisation of the ChNS in rodents and humans, we discovered that beside innervation of arteries, choroidal veins and choriocapillaris are also innervated, suggesting that the entire choroidal vasculature is under neural control. The numerous synapses together with calcitonin gene-related peptide (CGRP) vesicles juxtaposed to choroidal macrophages indicate a neuro-immune crosstalk. Using ultrastructural approaches, we show that transgenic mice overexpressing human MR, display a pachychoroid-like phenotype, with signs of choroidal neuropathy including myelin abnormalities, accumulation and enlargement of mitochondria and nerves vacuolization. Transcriptomic analysis of the RPE/choroid complex in the transgenic mice reveals regulation of corticoids target genes, known to intervene in nerve pathophysiology, such as Lcn2, rdas1/dexras1, S100a8 and S100a9, rabphilin 3a (Rph3a), secretogranin (Scg2) and Kinesin Family Member 5A (Kif5a). Genes belonging to pathways related to vasculature development, hypoxia, epithelial cell apoptosis, epithelial mesenchymal transition, and inflammation, support the pachychoroid phenotype and highlight downstream molecular targets. Hypotheses on the imaging phenotype of pachychoroid in humans are put forward in the light of these new data. Our results provide evidence that MR overactivation causes a choroidal neuropathy that could explain the pachychoroid phenotype found in transgenic mice overexpressing human MR. In patients with pachychoroid and CSCR in which systemic dysautonomia has been demonstrated, MR-induced choroidal neuropathy could be the missing link between corticoids and pachychoroid.

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“…The inhibition of RPH3A could aggravate brain injury. Therefore, the increase in RPH3A may be an endogenous protective mechanism against brain injury [ 39 ]. RPH3A was also shown to be a novel target for levodopa-induced dyskinesias [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

A Metabolic Plasticity-Based Signature for Molecular Classification and Prognosis of Lower-Grade Glioma

Yang

Wu²,

Sun³

et al. 2022

Brain Sciences

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Background: Glioma is one of the major health problems worldwide. Biomarkers for predicting the prognosis of Glioma are still needed. Methods: The transcriptome data and clinic information on Glioma were obtained from the CGGA, TCGA, GDC, and GEO databases. The immune infiltration status in the clusters was compared. The genes with differential expression were identified, and a prognostic model was developed. Several assays were used to detect RPH3A’s role in Glioma cells, including CCK-8, colony formation, wound healing, and transwell migration assay. Results: Lower Grade Glioma (LGG) was divided into two clusters. The immune infiltration difference was observed between the two clusters. We screened for genes that differed between the two groups. WGCNA was used to construct a co-expressed network using the DEGs, and four co-expressed modules were identified, which are blue, green, grey, and yellow modules. High-risk patients have a lower overall survival rate than low-risk patients. In addition, the risk score is associated with histological subtypes. Finally, the role of RPH3A was detected. The overexpression of RPH3A in LGG cells can significantly inhibit cell proliferation and migration and regulate EMT-regulated proteins. Conclusion: Our study developed a metabolic-related model for the prognosis of Glioma cells. RPH3A is a potential therapeutic target for Glioma.

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Role of Rph3A in brain injury induced by experimental cerebral ischemia‐reperfusion model in rats

Cited by 14 publications

References 51 publications

Identification and Experimental Validation of Parkinson’s Disease with Major Depressive Disorder Common Genes

Identification and Experimental Validation of Parkinson’s Disease with Major Depressive Disorder Common Genes

The choroidal nervous system: a link between mineralocorticoid receptor and pachychoroid

A Metabolic Plasticity-Based Signature for Molecular Classification and Prognosis of Lower-Grade Glioma

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