Evidence map›Paper›PMID 28126896›Full record

ArticleSchizophrenia bulletin2017

Postsynaptic Density-95 Isoform Abnormalities in Schizophrenia.

Adam J Funk, Catharine A Mielnik, Rachael Koene, Erin Newburn, Amy J Ramsey, Barbara K Lipska, Robert E McCullumsmith

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Schizophrenia bulletin, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 5 pooled it
1.2field-weighted citation impact, top 21% 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

20 citing papers in PubMed, 5 syntheses or guidelines pooled it, 37 citations in OpenAlex.

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  16. Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases.International journal of molecular sciences · 2021
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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

7 authors at 4 institutions in 2 countries.

Adam J FunkDepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH.
Catharine A MielnikDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Rachael KoeneDepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH.
Erin NewburnPersonalis Inc., Menlo Park, CA.
Amy J RamseyDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Barbara K LipskaHuman Brain Collection Core, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD.
Robert E McCullumsmithDepartment of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH.
University of Cincinnati Medical Center · USUniversity of Toronto · CANational Institutes of Health · USPersonalis (United States) · US

Funding

Procurement and Characterization of Postmortem Brain TissueZICMH002903 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MARENCO, STEFANO · 2009 to 2025
$56.0M
Cell-specific analysis of sub-kinomes in schizophreniaR01MH107487 · NIMH · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI MCCULLUMSMITH, ROBERT E, MELLER, JAREK · 2016 to 2020
$1.9M
Defects of subcellular glutamate transporter localization in schizophreniaR01MH094445 · NIMH · UNIVERSITY OF CINCINNATI · PI MCCULLUMSMITH, ROBERT E · 2011 to 2015
$1.7M
Proteomic analysis of the postsynaptic density-95 interactome in schizophreniaR21MH107916 · NIMH · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI MCCULLUMSMITH, ROBERT E · 2016 to 2017
$434k
NIMH NIH HHS R01 MH094445NIMH NIH HHS R01 MH107487NIMH NIH HHS R21 MH107916
6 · The paper itself

Abstract

Background: Postsynaptic density-95 (PSD-95) protein expression is dysregulated in schizophrenia in a variety of brain regions. We have designed experiments to examine PSD-95 mRNA splice variant expression in the dorsolateral prefrontal cortex from subjects with schizophrenia. Methods: We performed quantitative PCR and western blot analysis to measure PSD-95 expression in schizophrenia vs control subjects, rodent haloperidol treatment studies, rodent postmortem interval studies, and GluN1 knockdown (KD) mice vs controls. Results: We found decreased mRNA expression of beta (t = 4.506, df = 383, P < .0001) and truncated (t = 3.378, df = 383, P = .0008) isoforms of PSD-95, whereas alpha was unchanged. Additionally, we found decreased PSD-95 protein expression in schizophrenia (t = 2.746, df = 71, P = .0076). We found no correlation between PSD-95 protein and alpha, beta, or truncated mRNA isoforms in schizophrenia. PSD-95 beta transcript was increased (t = 3.346, df = 14, P < .05) in the GluN1 KD mouse model of schizophrenia. There was an increase in PSD-95 alpha mRNA expression (t = 2.905, df = 16, P < .05) in rats following long-term haloperidol administration. Conclusions: Our findings describe a unique pathophysiology of specific PSD-95 isoform dysregulation in schizophrenia, chronic neuroleptic treatment, and a genetic lesion mouse model of drastically reduced N-methyl-d-aspartate receptor (NMDAR) complex expression. These data indicate that regulation of PSD-95 is multifaceted, may be isoform specific, and biologically relevant for synaptic signaling function. Specifically, NMDAR-mediated synaptic remodeling, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking and interaction may be impaired in schizophrenia by decreased PSD-95 beta and truncated expression (respectively). Further, increased PSD-95 beta transcript in the GluN1 KD mouse model poses a potential compensatory rescue of NMDAR-mediated function via increased postsynaptic throughput of the severely reduced GluN1 signal. Together, these data propose that disruption of excitatory signaling complexes through genetic (GluN1 KD), pharmacologic (antipsychotics), or disease (schizophrenia) mechanisms specifically dysregulates PSD-95 expression.

Indexed as

RNA Splice SitesAdultAgedAnimalsAntipsychotic AgentsDisease Models, AnimalDisks Large Homolog 4 ProteinFemaleHaloperidolHumansMaleMiceMice, TransgenicMiddle AgedNerve Tissue ProteinsPrefrontal CortexAntipsychotic AgentsDisks Large Homolog 4 ProteinGprin1 protein, mouseHaloperidolNerve Tissue ProteinsProtein IsoformsReceptors, N-Methyl-D-AspartateRNA Splice SitesisoformmRNApostmortemproteinPSD-95schizophreniasplice variant

Identifiers

PMID28126896
PMCPMC5472126
OpenAlexW2582404868

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.