Evidence map›Paper›PMID 31570775›Full record

ArticleMolecular psychiatry2020

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

Ming Ren, Zhonghua Hu, Qiang Chen, Andrew Jaffe, Yingbo Li, Vijay Sadashivaiah, Shujuan Zhu, Nina Rajpurohit, Joo Heon Shin, Wei Xia and 14 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Trial
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  9. Analysis ofGenes · 2022
    Article
  10. Article
  11. Article
  12. The ERG1 KFrontiers in molecular neuroscience · 2022
    Review
  13. Review
  14. Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 3 institutions in 2 countries.

Ming Ren *Lieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Zhonghua Hu *Lieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Qiang Chen *Lieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Andrew JaffeLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-6886-1454
Yingbo LiLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Vijay SadashivaiahLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-1619-4471
Shujuan ZhuLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Nina RajpurohitLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Joo Heon ShinLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Wei XiaLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Yankai JiaLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Jingxian WuLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Sunny Lang QinLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Xinjian LiUnit on Neural Circuits and Adaptive Behaviours, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Bethesda, MD, USA.
Jian ZhuLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Qingjun TianLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Daniel ParedesLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Fengyu ZhangLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8504-0770
Kuan Hong WangUnit on Neural Circuits and Adaptive Behaviours, Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2249-5417
Venkata S MattayLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Joseph H CallicottSection on Integrative Neuroimaging and the Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD, USA.
Karen F BermanSection on Integrative Neuroimaging and the Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD, USA.
Daniel R WeinbergerLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA. drweinberger@libd.org.ORCID http://orcid.org/0000-0003-2409-2969
Feng YangLieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, MD, USA. yangf1979p2@qq.com.ORCID http://orcid.org/0000-0003-1275-6641
Johns Hopkins University · USNational Institute of Mental Health · USCentral South University · CN

Funding

Multimodal Imaging: Genetic and Environmental Effects in NeuropsychiatryZIAMH002942 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI BERMAN, KAREN FAITH · 2013 to 2022
$12.2M
KCNH2-3.1 potassium channel and schizophrenia.R01MH101102 · NIMH · LIEBER INSTITUTE, INC. · PI YANG, FENG · 2014 to 2018
$1.5M
6 · The paper itself

Abstract

Increased expression of the 3.1 isoform of the KCNH2 potassium channel has been associated with cognitive dysfunction and with schizophrenia, yet little is known about the underlying pathophysiological mechanisms. Here, by using in vivo wireless local field potential recordings during working memory processing, in vitro brain slice whole-cell patching recordings and in vivo stereotaxic hippocampal injection of AAV-encoded expression, we identified specific and delayed disruption of hippocampal-mPFC synaptic transmission and functional connectivity associated with reductions of SERPING1, CFH, and CD74 in the KCNH2-3.1 overexpression transgenic mice. The differentially expressed genes in mice are enriched in neurons and microglia, and reduced expression of these genes dysregulates the complement cascade, which has been previously linked to synaptic plasticity. We find that knockdown of these genes in primary neuronal-microglial cocultures from KCNH2-3.1 mice impairs synapse formation, and replenishing reduced CFH gene expression rescues KCNH2-3.1-induced impaired synaptogenesis. Translating to humans, we find analogous dysfunctional interactions between hippocampus and prefrontal cortex in coupling of the fMRI blood oxygen level-dependent (BOLD) signal during working memory in healthy subjects carrying alleles associated with increased KCNH2-3.1 expression in brain. Our data uncover a previously unrecognized role of the truncated KCNH2-3.1 potassium channel in mediating complement activation, which may explain its association with altered hippocampal-prefrontal connectivity and synaptic function. These results provide a potential molecular link between increased KCNH2-3.1 expression, synapse alterations, and hippocampal-prefrontal circuit abnormalities implicated in schizophrenia.

Indexed as

AnimalsBrainCognitive DysfunctionComplement ActivationERG1 Potassium ChannelFemaleHippocampusHumansMagnetic Resonance ImagingMaleMemory DisordersMemory, Short-TermMiceMice, Inbred C57BLMice, TransgenicNeuronal PlasticityERG1 Potassium ChannelKCNH2 protein, human

Identifiers

PMID31570775
OpenAlexW2974959638

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.