Evidence map›Paper›PMID 30391323›Full record

ArticleNeuroscience letters2019

Neuronal serine racemase associates with Disrupted-In-Schizophrenia-1 and DISC1 agglomerates: Implications for schizophrenia.

Ariel A Jacobi, Sarah Halawani, David R Lynch, Hong Lin

Abstract read
In one paragraph

Article in Neuroscience letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. d-Amino Acids and pLG72 in Alzheimer's Disease and Schizophrenia.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Review
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

4 authors at 2 institutions in 1 country.

Ariel A JacobiDepartment of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, 19104, United States.
Sarah HalawaniChildren's Hospital of Philadelphia, Philadelphia, PA, 19104, United States.
David R LynchDepartments of Pediatrics and Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, United States; Children's Hospital of Philadelphia, Philadelphia, PA, 19104, United States.
Hong LinDepartments of Pediatrics and Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, United States; Children's Hospital of Philadelphia, Philadelphia, PA, 19104, United States. Electronic address: linh@email.chop.edu.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · US

Funding

The Intellectual and Developmental Disabilities Research Center at CHOP/PennU54HD086984 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI SCHULTZ, ROBERT THOMAS · 2016 to 2020
$6.3M
Regulation of NMDA Receptors in Excitotoxicity by Calpain and FYNR01NS045986 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI LYNCH, DAVID ROBINSON · 2003 to 2011
$2.9M
Nicotinic-glutamatergic Interactions in Axonal DevelopmentR21NS072842 · NINDS · CHILDREN'S HOSP OF PHILADELPHIA · PI LYNCH, DAVID ROBINSON · 2011 to 2012
$444k
NICHD NIH HHS U54 HD086984NINDS NIH HHS R01 NS045986NINDS NIH HHS R21 NS072842
6 · The paper itself

Abstract

D-Serine, an endogenous coagonist of N-methyl-d-aspartate receptors (NMDARs) at the glycine binding site, is synthesized by serine racemase (SR) through conversion of l-Serine. Dysregulation of SR/D-Serine and Disrupted-In-Schizophrenia-1 (DISC1) contributes to the pathogenesis of schizophrenia at converging pathways, as perturbation of SR-DISC1 binding in astrocytes elicits schizophrenia-like behaviors in mice. However, an association of neuronal SR with DISC1 remains elusive. Here we report that SR associates with DISC1 and its agglomerates in cortical neurons, which can be modulated by NMDAR activity. Endogenous SR colocalizes with DISC1 large agglomerates in the soma and with smaller puncta in the nucleus and dendrites of cortical neurons. Co-immunoprecipitation assays demonstrate SR interaction with DISC1 in cortical neuronal lysates, suggesting the physiological presence of functional SR-DISC1 complexes in neurons. Moreover, exogenous d-Serine application significantly increases the interaction of SR with DISC1, the number of DISC1-SR large agglomerates and the levels of DISC1 agglomerated form along with SR in the triton-insoluble pellet fraction, whereas application of glycine with a glycine transporter inhibitor fails to increase their interactions, abundance of DISC1-SR large agglomerates and levels of DISC1 agglomerated form. This increase by d-Serine application is blocked by 7-chlorokynurenic acid, a specific antagonist at the glycine site of NMDARs, suggesting mediation through NMDARs. Our findings thus demonstrate neuronal SR association with DISC1 and its agglomerates, which can be modulated by d-Serine, thereby validating a novel neuronal SR-DISC1 complex responsive to NMDAR activation and providing a molecular mechanism by which pathways implicated in schizophrenia converge.

Indexed as

AnimalsCell NucleusCerebral CortexDendritesImmunoprecipitationMice, Inbred C57BLNerve Tissue ProteinsNeuronsPrimary Cell CultureRacemases and EpimerasesSchizophreniaSerine RacemaseDisc1 protein, mouseNerve Tissue ProteinsRacemases and EpimerasesSerine RacemaseAgglomeratesCortical neuronsDisrupted-In-Schizophrenia-1d-SerineNMDA receptorSerine racemase

Identifiers

PMID30391323
PMCPMC6402792
OpenAlexW2898784992

What OpenQuestion holds

Textmetadata
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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.