Hdl Handle:
http://hdl.handle.net/10675.2/742
Title:
Long-Term Continuous Corticosterone Treatment Decreases VEGF Receptor-2 Expression in Frontal Cortex
Authors:
Howell, Kristy R. ( 0000-0002-0872-5335 ) ; Kutiyanawalla, Ammar; Pillai, Anilkumar
Abstract:
Objective: Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated.; Material and Methods: We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects.; Results: We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects.; Conclusions: The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecular mechanism of the neurobiological effects of chronic stress.
Citation:
PLoS One. 2011 May 27; 6(5):e20198
Issue Date:
27-May-2011
URI:
http://hdl.handle.net/10675.2/742
DOI:
10.1371/journal.pone.0020198
PubMed ID:
21647420
PubMed Central ID:
PMC3103541
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Psychiatry and Health Behavior: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorHowell, Kristy R.en_US
dc.contributor.authorKutiyanawalla, Ammaren_US
dc.contributor.authorPillai, Anilkumaren_US
dc.date.accessioned2012-10-26T20:27:54Z-
dc.date.available2012-10-26T20:27:54Z-
dc.date.issued2011-05-27en_US
dc.identifier.citationPLoS One. 2011 May 27; 6(5):e20198en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21647420en_US
dc.identifier.doi10.1371/journal.pone.0020198en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/742-
dc.description.abstractObjective: Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated.en_US
dc.description.abstractMaterial and Methods: We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects.en_US
dc.description.abstractResults: We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects.en_US
dc.description.abstractConclusions: The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecular mechanism of the neurobiological effects of chronic stress.en_US
dc.rightsHowell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectMedicineen_US
dc.subjectMental Healthen_US
dc.subjectPsychiatryen_US
dc.subjectAnxiety Disordersen_US
dc.subjectNeuropsychiatric Disordersen_US
dc.subjectSchizophreniaen_US
dc.titleLong-Term Continuous Corticosterone Treatment Decreases VEGF Receptor-2 Expression in Frontal Cortexen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3103541en_US
dc.contributor.corporatenameDepartment of Psychiatry and Health Behavior-
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