Brain-derived neurotropic factor (BDNF) promotes molecular polarization and differentiation of immature neuroblastoma cells into definitive neurons

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F20%3A43920234" target="_blank" >RIV/00023752:_____/20:43920234 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/20:43920136

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0167488920300951" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0167488920300951</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbamcr.2020.118737" target="_blank" >10.1016/j.bbamcr.2020.118737</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Brain-derived neurotropic factor (BDNF) promotes molecular polarization and differentiation of immature neuroblastoma cells into definitive neurons

Popis výsledku v původním jazyce

Throughout development, neuronal progenitors undergo complex transformation into polarized nerve cells, warranting the directional flow of information in a neural grid. The majority of neuronal polarization studies have been carried out on rodent-derived precursor cells, programmed to develop into neurons. Unlike these rodent neuronal cells, SH-SY5Y cells derived from human bone marrow present a sub-clone of neuroblastoma line, with transformation into neuron-like cells showing a range of highly instructive neurobiological characteristics. We applied two-step retinoic acid (RA) and brain-derived neurotrophic factor (BDNF) protocol to monitor the conversion of undifferentiated SH-SY5Y cells into neuron-like cells with distinctly polarized axon-dendritic morphology and formation of bona fide synaptic connections. We show that BDNF is a key driver and regulator of the expression of axonal marker tau and dendritic microtubule-associated protein-2 (MAP2), with their sorting to distinct cellular compartments. Using selective kinase inhibitors downregulating BDNF-TrkB signaling, we show that constitutive activation of TrkB receptor is essential for the maintenance of established polarization of SH-SY5Y cells. Importantly, the proximity ligation assay applied in our preparation demonstrates that differentiating neuron-like cells develop elaborate synaptic connections enriched with hallmark pre- and postsynaptic proteins. Described herein observations highlight several fundamental processes related to neuronal polarization and synaptogenesis in human-derived cells, which are of major relevance to neuronal biology, neurodevelopment, and translational neuroscience.

Název v anglickém jazyce

Brain-derived neurotropic factor (BDNF) promotes molecular polarization and differentiation of immature neuroblastoma cells into definitive neurons

Popis výsledku anglicky

Throughout development, neuronal progenitors undergo complex transformation into polarized nerve cells, warranting the directional flow of information in a neural grid. The majority of neuronal polarization studies have been carried out on rodent-derived precursor cells, programmed to develop into neurons. Unlike these rodent neuronal cells, SH-SY5Y cells derived from human bone marrow present a sub-clone of neuroblastoma line, with transformation into neuron-like cells showing a range of highly instructive neurobiological characteristics. We applied two-step retinoic acid (RA) and brain-derived neurotrophic factor (BDNF) protocol to monitor the conversion of undifferentiated SH-SY5Y cells into neuron-like cells with distinctly polarized axon-dendritic morphology and formation of bona fide synaptic connections. We show that BDNF is a key driver and regulator of the expression of axonal marker tau and dendritic microtubule-associated protein-2 (MAP2), with their sorting to distinct cellular compartments. Using selective kinase inhibitors downregulating BDNF-TrkB signaling, we show that constitutive activation of TrkB receptor is essential for the maintenance of established polarization of SH-SY5Y cells. Importantly, the proximity ligation assay applied in our preparation demonstrates that differentiating neuron-like cells develop elaborate synaptic connections enriched with hallmark pre- and postsynaptic proteins. Described herein observations highlight several fundamental processes related to neuronal polarization and synaptogenesis in human-derived cells, which are of major relevance to neuronal biology, neurodevelopment, and translational neuroscience.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/LO1611" target="_blank" >LO1611: Udržitelnost pro Národní ústav duševního zdraví</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biochimica et Biophysica Acta-Molecular Cell Research

ISSN

0167-4889

e-ISSN

—

Svazek periodika

1867

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

11

Strana od-do

"Article Number: 118737"

Kód UT WoS článku

000540698600007

EID výsledku v databázi Scopus

2-s2.0-85085179516