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Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons

A hallmark of glioblastoma multiforme (GBM) is neoangiogenesis, mediated by the overexpression of vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, like bevacizumab, prolong progression-free survival in GBM, however, this treatment has been reported to be associated with a decline in...

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Autores principales: Latzer, Pauline, Shchyglo, Olena, Hartl, Tim, Matschke, Veronika, Schlegel, Uwe, Manahan-Vaughan, Denise, Theiss, Carsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445260/
https://www.ncbi.nlm.nih.gov/pubmed/30971896
http://dx.doi.org/10.3389/fncel.2019.00113
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author Latzer, Pauline
Shchyglo, Olena
Hartl, Tim
Matschke, Veronika
Schlegel, Uwe
Manahan-Vaughan, Denise
Theiss, Carsten
author_facet Latzer, Pauline
Shchyglo, Olena
Hartl, Tim
Matschke, Veronika
Schlegel, Uwe
Manahan-Vaughan, Denise
Theiss, Carsten
author_sort Latzer, Pauline
collection PubMed
description A hallmark of glioblastoma multiforme (GBM) is neoangiogenesis, mediated by the overexpression of vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, like bevacizumab, prolong progression-free survival in GBM, however, this treatment has been reported to be associated with a decline in neurocognitive function. Therefore, this study focused on the effects of bevacizumab on neuronal function and plasticity. We analyzed neuronal membrane properties and synaptic plasticity in rat hippocampal slices, as well as spine dynamics in dissociated hippocampal neurons, to examine the impact of bevacizumab on hippocampal function and viability. VEGF inhibition resulted in profound impairments in hippocampal synaptic plasticity as well as reductions in dendritic spine number and length. Physiological properties of hippocampal neurons were also affected. These effects of VEGF blockade on hippocampal function may play a role in compromising memory and information processing and thus, may contribute to neurocognitive dysfunction in GBM patients treated with bevacizumab.
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spelling pubmed-64452602019-04-10 Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons Latzer, Pauline Shchyglo, Olena Hartl, Tim Matschke, Veronika Schlegel, Uwe Manahan-Vaughan, Denise Theiss, Carsten Front Cell Neurosci Neuroscience A hallmark of glioblastoma multiforme (GBM) is neoangiogenesis, mediated by the overexpression of vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, like bevacizumab, prolong progression-free survival in GBM, however, this treatment has been reported to be associated with a decline in neurocognitive function. Therefore, this study focused on the effects of bevacizumab on neuronal function and plasticity. We analyzed neuronal membrane properties and synaptic plasticity in rat hippocampal slices, as well as spine dynamics in dissociated hippocampal neurons, to examine the impact of bevacizumab on hippocampal function and viability. VEGF inhibition resulted in profound impairments in hippocampal synaptic plasticity as well as reductions in dendritic spine number and length. Physiological properties of hippocampal neurons were also affected. These effects of VEGF blockade on hippocampal function may play a role in compromising memory and information processing and thus, may contribute to neurocognitive dysfunction in GBM patients treated with bevacizumab. Frontiers Media S.A. 2019-03-26 /pmc/articles/PMC6445260/ /pubmed/30971896 http://dx.doi.org/10.3389/fncel.2019.00113 Text en Copyright © 2019 Latzer, Shchyglo, Hartl, Matschke, Schlegel, Manahan-Vaughan and Theiss. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Latzer, Pauline
Shchyglo, Olena
Hartl, Tim
Matschke, Veronika
Schlegel, Uwe
Manahan-Vaughan, Denise
Theiss, Carsten
Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons
title Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons
title_full Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons
title_fullStr Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons
title_full_unstemmed Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons
title_short Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons
title_sort blocking vegf by bevacizumab compromises electrophysiological and morphological properties of hippocampal neurons
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445260/
https://www.ncbi.nlm.nih.gov/pubmed/30971896
http://dx.doi.org/10.3389/fncel.2019.00113
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