Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.

MK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and thei...

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Main Authors: Wenjuan Yu, Hao Zhu, Yueming Wang, Guanjun Li, Lihua Wang, Huafang Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145651&type=printable
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author Wenjuan Yu
Hao Zhu
Yueming Wang
Guanjun Li
Lihua Wang
Huafang Li
author_facet Wenjuan Yu
Hao Zhu
Yueming Wang
Guanjun Li
Lihua Wang
Huafang Li
author_sort Wenjuan Yu
collection DOAJ
description MK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and their significance to schizotypic symptoms are unclear. Changes in the expression levels of glial fibrillary acid protein (GFAP), a marker of astrocyte activation in response to a variety of pathogenic stimuli, were examined in the hippocampus of rats treated with the repeated MK-801 injection (0.5 mg/10 ml/kg body weight for 6 days) and in primary cultured hippocampal astrocytes incubated with MK-801 (5 or 20 μM for 24 h). Moreover, the expression levels of BDNF and its receptors TrkB and p75 were examined in MK-801-treated astrocyte cultures. MK-801 treatment enhanced GFAP expression in the rat hippocampus and also increased the levels of GFAP protein and mRNA in hippocampal astrocytes in vitro. Treatment of cultured hippocampal astrocytes with MK-801 enhanced protein and mRNA levels of BDNF, TrkB, and p75. Collectively, our results suggest that hippocampal astrocytes may contribute to the pathophysiology of schizophrenia symptoms associated with NMDA receptor hypofunction by reactive transformation and altered BDNF signaling.
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spelling doaj-art-132e56905e4e44249ba024c4cd2fe5c42025-08-20T03:10:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014565110.1371/journal.pone.0145651Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.Wenjuan YuHao ZhuYueming WangGuanjun LiLihua WangHuafang LiMK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and their significance to schizotypic symptoms are unclear. Changes in the expression levels of glial fibrillary acid protein (GFAP), a marker of astrocyte activation in response to a variety of pathogenic stimuli, were examined in the hippocampus of rats treated with the repeated MK-801 injection (0.5 mg/10 ml/kg body weight for 6 days) and in primary cultured hippocampal astrocytes incubated with MK-801 (5 or 20 μM for 24 h). Moreover, the expression levels of BDNF and its receptors TrkB and p75 were examined in MK-801-treated astrocyte cultures. MK-801 treatment enhanced GFAP expression in the rat hippocampus and also increased the levels of GFAP protein and mRNA in hippocampal astrocytes in vitro. Treatment of cultured hippocampal astrocytes with MK-801 enhanced protein and mRNA levels of BDNF, TrkB, and p75. Collectively, our results suggest that hippocampal astrocytes may contribute to the pathophysiology of schizophrenia symptoms associated with NMDA receptor hypofunction by reactive transformation and altered BDNF signaling.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145651&type=printable
spellingShingle Wenjuan Yu
Hao Zhu
Yueming Wang
Guanjun Li
Lihua Wang
Huafang Li
Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.
PLoS ONE
title Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.
title_full Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.
title_fullStr Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.
title_full_unstemmed Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.
title_short Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.
title_sort reactive transformation and increased bdnf signaling by hippocampal astrocytes in response to mk 801
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145651&type=printable
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