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 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.

Metadaten
Author:	Pauline Latzer GND, Olena Shchyglo GND, Tim Hartl GND, Veronika Matschke ORCiD GND, Uwe Schlegel GND, Denise Manahan-Vaughan ORCiD GND, Carsten Theiß ORCiD GND
URN:	urn:nbn:de:hbz:294-67049
DOI:	https://doi.org/10.3389/fncel.2019.00113
Parent Title (English):	Frontiers in cellular neuroscience
Publisher:	Frontiers Research Foundation
Place of publication:	Lausanne
Document Type:	Article
Language:	English
Date of Publication (online):	2019/11/12
Date of first Publication:	2019/03/26
Publishing Institution:	Ruhr-Universität Bochum, Universitätsbibliothek
Tag:	LTP; Open Access Fonds; bevacizumab; hippocampus; neuronal function; spines
Volume:	13
Issue:	Article 113
First Page:	113-1
Last Page:	113-10
Note:	Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:	Institut für Anatomie, Abteilung für Anatomie und Molekulare Embryologie
	Institut für Anatomie, Abteilung für Cytologie
	Knappschaftskrankenhaus Bochum, Klinik für Neurologie
	Abteilung für Neurophysiologie, Learning and Memory
open_access (DINI-Set):	open_access
faculties:	International Graduate School of Neuroscience (IGSN)
Licence (English):	Creative Commons - CC BY 4.0 - Attribution 4.0 International

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