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The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory
AuthorMonje, Francisco J. ; Uhrin, Pavel ; Pollak, Daniela D. ; Kerjaschki, Dontscho ; Breuss, Johannes M. ; Smani, Tarik ; Milicevic, Radoslav ; Aguilar, Juan Pablo Acevedo ; Molz, Barbara ; Cabatic, Maureen ; Dominguez-Rodriguez, Manuel ; Kim, Eun-Jung ; Khan, Deeba ; Krieger, Sigurd ; Yang, Jiaye ; Cicvaric, Ana
Published in
Annals of Medicine, Abingdon, 2016, Vol. 48, Issue 8, page 652-668
PublishedAbingdon : Taylor & Francis, 2016
Document typeJournal Article
Keywords (EN)podoplanin / ezrin / dentate gyrus / hippocampus / neuron / synaptic plasticity / memory / nerve growth factor / factor gene-therapy / alzheimers-disease / mouse hippocampus / cells / receptors / expression / ngf / presenilin-1/gamma-secretase / neurodegeneration
Project-/ReportnumberP 27551-B27
URNurn:nbn:at:at-ubmuw:3-1146 Persistent Identifier (URN)
 The work is publicly available
The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory [3.08 mb]
Abstract (English)

Introduction: Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Materials and methods: Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Results:Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. Discussion: This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology.

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