KCNH2-3.1 mediates aberrant complement activation and impaired hippocampal-medial prefrontal circuitry associated with working memory deficits

Ren, Ming; Hu, Zhonghua; Chen, Qiang; Jaffe, Andrew E.; Li, Yingbo; Sadashivaiah, Vijay; Zhu, Shaojun; Rajpurohit, Nina; Shin, Joo Heon; Jia, Yankai; Wu, Jiangling; Qin, Sunny Lang; Li, Xinjian; Zhu, Jie; Tian, Qingjun; Paredes, Daniel; Zhang, Fengyu; Wang, Kuan Hong; Mattay, Venkata S.; Callicott, Joseph H.; Berman, Karen F.; Weinberger, Daniel R.; Yang, Feng

doi:10.1038/s41380-019-0530-1

Cited by 16 publications

(13 citation statements)

References 94 publications

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“…Studies have also reported that CHRFAM7A [58], ACHE (acetylcholinesterase (Cartwright blood group) [305], HP (haptoglobin) [306], SELENBP1 [63], BASP1 [72], CHRNA1 [307], RPTN (repetin) [76], IL33 [308], TACR1[309], SHANK3 [310], ALOX12B [311], HPN (hepsin) [312], GFAP (glial fibrillary acidic protein) [84], CACNB2 [313], MYT1 [314], NOTCH3 [315], TERT (telomerase reverse transcriptase) [316], GNB3 [317], EGR3 [318], BSN (bassoon presynaptic cytomatrix protein) [319], CUX2 [320], GDF15 [321], CXCL8 [322], MAGI1 [95] and PAH (phenylalanine hydroxylase) [323] are necessary for BD development. S100A12 [324], CDH1 [325], S100A9 [326], ANK1 [327], KCNH2 [328], HP (haptoglobin) [329], FRMD4A [330], SNCA (synuclein alpha) [331], FBXO7 [332], PINK1 [333], B2M [334], KCNH3 [335], CA2 [336], FUZ (fuzzy planar cell polarity protein) [337], UBB (ubiquitin B) [338], C5AR1 [339], CBS (cystathionine beta-synthase) [340], F12 [341], TSPAN5 [342], NQO2 [343], NDUFA1 [344], SRXN1 [345], BASP1 [346], GPX1 [347], OLIG2 [348], EFHC2 [349], FOXA1 [350], PAX4 [351], BGN (biglycan) [352], IL33 [353], LRIG3 [354], GJA1 [355], SHANK3 [356], ARC (activity regulated cytoskeleton associated protein) [357], GFAP (glial fibrillary acidic protein) [358], UNC13A [359], MSTN (myostatin) [360], HSPG2 [361], TERT (telomerase reverse transcriptase) [362], GNB3 [363], L1CAM [364], CALB1 [365], RYR2 [366], MYO15A [367], MYH11 [368], GDF15 […”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Bipolar disorder (BD), also known as psychiatric disorder, affects millions of people all over the world. The aim of this investigation was to screen and verify hub genes involved in BD as well as to explore potential molecular mechanisms. The next generation sequencing (NGS) dataset GSE124326 was downloaded from the Gene Expression Omnibus (GEO) database, which contained 480 samples, including 240 BD and 240 normal controls. Differentially expressed genes (DEGs) were filtered and subjected to gene ontology (GO) and pathway enrichment analyses. A protein–protein interaction (PPI) network and module analysis were used to identify hub genes. The miRNA-hub gene regulatory network and TF-hub gene regulatory network were also constructed. Receiver operating characteristic curve (ROC) analysis was used to validate hub genes. In this work, 957 DEGs, including 477 up regulated and 480 down regulated, were obtained from NGS data. The GO and pathway enrichment analyses of the DEGs showed that the up regulated genes were enriched in the neutrophil degranulation, immune system, transport, cytoplasm and enzyme regulator activity, and the down regulated genes were enriched in extracellular matrix organization, diseases of metabolism, multicellular organismal process, cell periphery and metal ion binding. Finally, through analyzing the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, we screened hub genes UBB, UBE2D1, TUBA1A, RPL11, RPS24, NOTCH3, CAV1, CNBD2, CCNA1 and MYH11 by the Cytoscape software. The current investigation illustrates a characteristic NGS data in BD, which might contribute to the interpretation of the progression of BD and provide novel biomarkers and therapeutic targets for BD.

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Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad¹,

Vastrad²

2022

Preprint

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“…This gene encodes a plasma protein involved in the regulation of the complement cascade. This cascade has been related to synaptic plasticity, as the knockdown of Serp-ing1 in mice impairs synapse formation [Ren et al, 2020]. The gene has been also linked to cortical development, particularly to neuronal migration [Gorelik et al, 2017].…”

Section: Discussionmentioning

confidence: 99%

Language Impairment with a Partial Duplication of DOCK8

2020

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Duplications of the distal region of the short arm of chromosome 9 are rare, but are associated with learning disabilities and behavioral disturbances. We report in detail the cognitive and language features of a child with a duplication in the 9p24.3 region, arr[hg19] 9p24.3(266,045–459,076)×3. The proband exhibits marked expressive and receptive problems, which affect both structural and functional aspects of language. These problems might result from a severe underlying deficit in working memory. Regarding the molecular causes of the observed symptoms, they might result from the altered expression of selected genes involved in procedural learning, particularly some of components of the SLIT/ROBO/FOXP2 network, strongly related to the development and evolution of language. Dysregulation of specific components of this network can result in turn from an altered interaction between DOCK8, affected by the microduplication, and CDC42, acting as the hub component of the network encompassing language-related genes.

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“…ERG1c is associated with cognitive dysfunction ( Huffaker et al, 2009 ; Calcaterra et al, 2016 ; Carr et al, 2016 ). ERG1a and ERG1b are expressed in both heart and brain, whereas ERG1c appears to be largely limited to the mammalian brain, particularly in the hippocampus ( Warmke and Ganetzky, 1994 ; Saganich et al, 2001 ; Guasti et al, 2005 ; Huffaker et al, 2009 ; Uhlen et al, 2015 ; Carr et al, 2016 ; Ren et al, 2020 ).…”

Section: Erg1 Structure and Functionmentioning

confidence: 99%

“…Because of this, ERG1c upregulation increases AP firing frequency and reduces spike frequency adaptation as seen in primary cortical neurons ( Huffaker et al, 2009 ). Complementary fMRI data in schizophrenic patients with genetic variants associated with increased ERG1c show analogous hippocampus-prefrontal cortex disruption ( Ren et al, 2020 ). In the context of drug treatment for schizophrenic patients, the antipsychotic Risperidone is a known ERG1c blocker and shows greater therapeutic efficacy in patients carrying genetic variants associated with upregulated ERG1c ( Heide et al, 2016 ).…”

Section: Erg1 In Neuronal Physiology and Pathophysiologymentioning

confidence: 99%

“…Other analyses of schizophrenic patients treated with antidopaminergic drugs also showcase higher therapeutic success in patients with genetic variants causing increased expression of ERG1c ( Apud et al, 2012 ). ERG1c is also linked to cognitive dysfunction, where ERG1c overexpression disrupts synaptic transmission and synapse formation between the hippocampus and prefrontal cortex in mice ( Carr et al, 2016 ; Ren et al, 2020 ). ERG1c overexpression also disrupts behavioral working memory tasks while ERG1c suppression rescues behavior and promotes synapse formation ( Carr et al, 2016 ).…”

Section: Erg1 In Neuronal Physiology and Pathophysiologymentioning

confidence: 99%

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The ERG1 K+ Channel and Its Role in Neuronal Health and Disease

Sanchez-Conde

Jiménez-Vázquez

Auerbach

et al. 2022

Front. Mol. Neurosci.

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The ERG1 potassium channel, encoded by KCNH2, has long been associated with cardiac electrical excitability. Yet, a growing body of work suggests that ERG1 mediates physiology throughout the human body, including the brain. ERG1 is a regulator of neuronal excitability, ERG1 variants are associated with neuronal diseases (e.g., epilepsy and schizophrenia), and ERG1 serves as a potential therapeutic target for neuronal pathophysiology. This review summarizes the current state-of-the-field regarding the ERG1 channel structure and function, ERG1’s relationship to the mammalian brain and highlights key questions that have yet to be answered.

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KCNH2-3.1 mediates aberrant complement activation and impaired hippocampal-medial prefrontal circuitry associated with working memory deficits

Cited by 16 publications

References 94 publications

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

Identification of Key Genes and Biological Pathways in Bipolar Disorder by Bioinformatics and Next Generation Sequencing Data Analysis

Language Impairment with a Partial Duplication of DOCK8

The ERG1 K+ Channel and Its Role in Neuronal Health and Disease

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