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

Overview of attention for article published in Molecular Neurobiology, May 2016
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Title
The Atypical Antipsychotic Agent, Clozapine, Protects Against Corticosterone-Induced Death of PC12 Cells by Regulating the Akt/FoxO3a Signaling Pathway
Published in
Molecular Neurobiology, May 2016
DOI 10.1007/s12035-016-9904-4
Pubmed ID
Authors

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

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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 14%
Student > Ph. D. Student 5 14%
Student > Bachelor 4 11%
Student > Doctoral Student 3 9%
Professor 2 6%
Other 4 11%
Unknown 12 34%
Readers by discipline Count As %
Neuroscience 5 14%
Pharmacology, Toxicology and Pharmaceutical Science 4 11%
Biochemistry, Genetics and Molecular Biology 3 9%
Nursing and Health Professions 2 6%
Sports and Recreations 2 6%
Other 6 17%
Unknown 13 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 May 2016.
All research outputs
#20,326,948
of 22,870,727 outputs
Outputs from Molecular Neurobiology
#2,796
of 3,463 outputs
Outputs of similar age
#266,104
of 312,377 outputs
Outputs of similar age from Molecular Neurobiology
#72
of 95 outputs
Altmetric has tracked 22,870,727 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,463 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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