Evidence map›Paper›PMID 27173157›Full record

ArticleMolecular neurobiology2017

The Atypical Antipsychotic Agent, Clozapine, Protects Against Corticosterone-Induced Death of PC12 Cells by Regulating the Akt/FoxO3a Signaling Pathway.

Zhiwen Zeng, Xue Wang, Sanjeev K Bhardwaj, Xuanhe Zhou, Peter J Little, Remi Quirion, Lalit K Srivastava, Wenhua Zheng

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. The role of Foxo3a in neuron-mediated cognitive impairment.Frontiers in molecular neuroscience · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
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  12. Article
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  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. HOncotarget · 2017
    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

8 authors at 5 institutions in 4 countries.

Zhiwen ZengFaculty of Health Sciences, University of Macau, Taipa, Macau, China.
Xue WangFaculty of Health Sciences, University of Macau, Taipa, Macau, China.
Sanjeev K BhardwajDouglas Hospital Research Center, McGill University, Montreal, Canada.
Xuanhe ZhouFaculty of Health Sciences, University of Macau, Taipa, Macau, China.
Peter J LittleSchool of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall St, Woolloongabba, QLD, 4102, Australia.
Remi QuirionDouglas Hospital Research Center, McGill University, Montreal, Canada.
Lalit K SrivastavaDouglas Hospital Research Center, McGill University, Montreal, Canada.
Wenhua ZhengFaculty of Health Sciences, University of Macau, Taipa, Macau, China. wenhuazheng@umac.mo.
Sun Yat-sen University · CNMcGill University · CADouglas Mental Health University Institute · CAUniversity of Macau · MOUniversity of Queensland · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Schizophrenia is one of the most severe psychiatric disorders. Increasing evidence implicates that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics are neuroprotective and successful in slowing the progressive morphological brain changes. As an antipsychotic agent, clozapine has superior and unique effects, but the intracellular signaling pathways that mediate clozapine action remain to be elucidated. The phosphatidylinositol-3-kinase/protein kinase B/Forkhead box O3 (PI3K/Akt/FoxO3a) pathway is crucial for neuronal survival. However, little information is available regarding this pathway with clozapine. In the present study, we investigated the protective effect of clozapine on the PC12 cells against corticosterone toxicity. Our results showed that corticosterone decreases the phosphorylation of Akt and FoxO3a, leading to the nuclear localization of FoxO3a and the apoptosis of PC12 cells, while clozapine concentration dependently protected PC12 cells against corticosterone insult. Pathway inhibitors studies displayed that the protective effect of clozapine was reversed by LY294002 and wortmannin, two PI3K inhibitors, or Akt inhibitor VIII although several other inhibitors had no effect. The shRNA knockdown results displayed that downregulated Akt1 or FoxO3a attenuated the protective effect of clozapine. Western blot analyses revealed that clozapine induced the phosphorylation of Akt and FoxO3a by the PI3K/Akt pathway and reversed the reduction of the phosphorylated Akt and FoxO3a and the nuclear translocation of FoxO3a evoked by corticosterone. Together, our data indicates that clozapine protects PC12 cells against corticosterone-induced cell death by modulating activity of the PI3K/Akt/FoxO3a pathway.

Indexed as

AnimalsAntipsychotic AgentsApoptosisCell DeathCell NucleusCell SurvivalChromonesClozapineCorticosteroneCytoprotectionFlavonoidsForkhead Box Protein O3Gene Knockdown TechniquesMorpholinesNeuroprotective AgentsPC12 Cells2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneAntipsychotic AgentsChromonesClozapineCorticosteroneFlavonoidsForkhead Box Protein O3FOXO3 protein, ratMorpholinesNeuroprotective AgentsPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktRNA, Small InterferingClozapineCorticosteroneNeuroprotectionPI3K/Akt/FoxO3aSchizophrenia

Identifiers

PMID27173157
OpenAlexW2358228273

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.