Neural stem cells modified to express BDNF antagonize trimethyltin-induced neurotoxicity through PI3K/Akt and MAP kinase pathways

Patrizia Casalbore, Ilaria Barone, Armando Felsani, Igea D'Agnano, Fabrizio Michetti, Giulio Maira, Carlo Cenciarelli

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

In vitro expansion of neural stem cells (NSC) lentivirally transduced with human BDNF may serve as better cellular source for replacing degenerating neurons in disease, trauma and toxic insults. In this study, we evaluate the functional role of forced BDNF expression by means of NSC (M3GFP-BDNF) obtained from cerebral cortex of 1-day-old mice respect to NSC-control (M3GFP).Wefind that M3GFP-BDNF induced to differentiate significantly accumulate BDNF and undergone to high potassium-mediated depolarization, show rapid BDNF recycle and activation of Trk receptors signaling. Differentiated M3GFP-BDNF exhibit neurons and oligodendrocytes with extended processes although quantitative analyses of NSC-derived cell lineages show none statistical significance between both cell populations. Moreover, those cells show a significant induction of neuronal and oligodendroglial markers by RT-PCR and Western blot respect to M3GFP, such as βIII-Tubulin, microtubule associated protein 2 (MAP2), neurofilaments heavy (NF-H), oligodendroglial myelin glycoprotein (OMG) and some molecules involved in glutamatergic synapse maturation, such as receptors tyrosine kinases (TRKs), postsynaptic density (PSD-95) and N-methyl-D-aspartate receptors 2 A/B (NMDA2A/B). After treatment with the neurotoxicant trimethyltin (TMT), differentiated M3GFP-BDNF exhibit an attenuation of cellular damage which correlates with a significant activation of MAPK and PI3K/Akt signaling and delayed activation of death signals, while on M3GFP, TMT induces a significant reduction of cell survival, neuronal differentiation and concomitant earlier activation of cleaved caspase-3. We demonstrate that overexpression of BDNF firmly regulate cell survival and differentiation of NSC and protects differentiated NSC against TMT-induced neurotoxicity through the PI3K/Akt and MAPK signaling pathways.

Original languageEnglish
Pages (from-to)710-721
Number of pages12
JournalJournal of Cellular Physiology
Volume224
Issue number3
DOIs
Publication statusPublished - Sep 2010

Fingerprint

Neural Stem Cells
Brain-Derived Neurotrophic Factor
Stem cells
Phosphatidylinositol 3-Kinases
Phosphotransferases
Chemical activation
Cells
Neurons
Cell Survival
Post-Synaptic Density
trimethyltin
Microtubule-Associated Proteins
Intermediate Filaments
Poisons
Oligodendroglia
Depolarization
Receptor Protein-Tyrosine Kinases
Cell Lineage
Tubulin
Myelin Sheath

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Neural stem cells modified to express BDNF antagonize trimethyltin-induced neurotoxicity through PI3K/Akt and MAP kinase pathways. / Casalbore, Patrizia; Barone, Ilaria; Felsani, Armando; D'Agnano, Igea; Michetti, Fabrizio; Maira, Giulio; Cenciarelli, Carlo.

In: Journal of Cellular Physiology, Vol. 224, No. 3, 09.2010, p. 710-721.

Research output: Contribution to journalArticle

Casalbore, Patrizia ; Barone, Ilaria ; Felsani, Armando ; D'Agnano, Igea ; Michetti, Fabrizio ; Maira, Giulio ; Cenciarelli, Carlo. / Neural stem cells modified to express BDNF antagonize trimethyltin-induced neurotoxicity through PI3K/Akt and MAP kinase pathways. In: Journal of Cellular Physiology. 2010 ; Vol. 224, No. 3. pp. 710-721.
@article{0efb46bc28c74e708ae453dade0427df,
title = "Neural stem cells modified to express BDNF antagonize trimethyltin-induced neurotoxicity through PI3K/Akt and MAP kinase pathways",
abstract = "In vitro expansion of neural stem cells (NSC) lentivirally transduced with human BDNF may serve as better cellular source for replacing degenerating neurons in disease, trauma and toxic insults. In this study, we evaluate the functional role of forced BDNF expression by means of NSC (M3GFP-BDNF) obtained from cerebral cortex of 1-day-old mice respect to NSC-control (M3GFP).Wefind that M3GFP-BDNF induced to differentiate significantly accumulate BDNF and undergone to high potassium-mediated depolarization, show rapid BDNF recycle and activation of Trk receptors signaling. Differentiated M3GFP-BDNF exhibit neurons and oligodendrocytes with extended processes although quantitative analyses of NSC-derived cell lineages show none statistical significance between both cell populations. Moreover, those cells show a significant induction of neuronal and oligodendroglial markers by RT-PCR and Western blot respect to M3GFP, such as βIII-Tubulin, microtubule associated protein 2 (MAP2), neurofilaments heavy (NF-H), oligodendroglial myelin glycoprotein (OMG) and some molecules involved in glutamatergic synapse maturation, such as receptors tyrosine kinases (TRKs), postsynaptic density (PSD-95) and N-methyl-D-aspartate receptors 2 A/B (NMDA2A/B). After treatment with the neurotoxicant trimethyltin (TMT), differentiated M3GFP-BDNF exhibit an attenuation of cellular damage which correlates with a significant activation of MAPK and PI3K/Akt signaling and delayed activation of death signals, while on M3GFP, TMT induces a significant reduction of cell survival, neuronal differentiation and concomitant earlier activation of cleaved caspase-3. We demonstrate that overexpression of BDNF firmly regulate cell survival and differentiation of NSC and protects differentiated NSC against TMT-induced neurotoxicity through the PI3K/Akt and MAPK signaling pathways.",
author = "Patrizia Casalbore and Ilaria Barone and Armando Felsani and Igea D'Agnano and Fabrizio Michetti and Giulio Maira and Carlo Cenciarelli",
year = "2010",
month = "9",
doi = "10.1002/jcp.22170",
language = "English",
volume = "224",
pages = "710--721",
journal = "Journal of cellular and comparative physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Neural stem cells modified to express BDNF antagonize trimethyltin-induced neurotoxicity through PI3K/Akt and MAP kinase pathways

AU - Casalbore, Patrizia

AU - Barone, Ilaria

AU - Felsani, Armando

AU - D'Agnano, Igea

AU - Michetti, Fabrizio

AU - Maira, Giulio

AU - Cenciarelli, Carlo

PY - 2010/9

Y1 - 2010/9

N2 - In vitro expansion of neural stem cells (NSC) lentivirally transduced with human BDNF may serve as better cellular source for replacing degenerating neurons in disease, trauma and toxic insults. In this study, we evaluate the functional role of forced BDNF expression by means of NSC (M3GFP-BDNF) obtained from cerebral cortex of 1-day-old mice respect to NSC-control (M3GFP).Wefind that M3GFP-BDNF induced to differentiate significantly accumulate BDNF and undergone to high potassium-mediated depolarization, show rapid BDNF recycle and activation of Trk receptors signaling. Differentiated M3GFP-BDNF exhibit neurons and oligodendrocytes with extended processes although quantitative analyses of NSC-derived cell lineages show none statistical significance between both cell populations. Moreover, those cells show a significant induction of neuronal and oligodendroglial markers by RT-PCR and Western blot respect to M3GFP, such as βIII-Tubulin, microtubule associated protein 2 (MAP2), neurofilaments heavy (NF-H), oligodendroglial myelin glycoprotein (OMG) and some molecules involved in glutamatergic synapse maturation, such as receptors tyrosine kinases (TRKs), postsynaptic density (PSD-95) and N-methyl-D-aspartate receptors 2 A/B (NMDA2A/B). After treatment with the neurotoxicant trimethyltin (TMT), differentiated M3GFP-BDNF exhibit an attenuation of cellular damage which correlates with a significant activation of MAPK and PI3K/Akt signaling and delayed activation of death signals, while on M3GFP, TMT induces a significant reduction of cell survival, neuronal differentiation and concomitant earlier activation of cleaved caspase-3. We demonstrate that overexpression of BDNF firmly regulate cell survival and differentiation of NSC and protects differentiated NSC against TMT-induced neurotoxicity through the PI3K/Akt and MAPK signaling pathways.

AB - In vitro expansion of neural stem cells (NSC) lentivirally transduced with human BDNF may serve as better cellular source for replacing degenerating neurons in disease, trauma and toxic insults. In this study, we evaluate the functional role of forced BDNF expression by means of NSC (M3GFP-BDNF) obtained from cerebral cortex of 1-day-old mice respect to NSC-control (M3GFP).Wefind that M3GFP-BDNF induced to differentiate significantly accumulate BDNF and undergone to high potassium-mediated depolarization, show rapid BDNF recycle and activation of Trk receptors signaling. Differentiated M3GFP-BDNF exhibit neurons and oligodendrocytes with extended processes although quantitative analyses of NSC-derived cell lineages show none statistical significance between both cell populations. Moreover, those cells show a significant induction of neuronal and oligodendroglial markers by RT-PCR and Western blot respect to M3GFP, such as βIII-Tubulin, microtubule associated protein 2 (MAP2), neurofilaments heavy (NF-H), oligodendroglial myelin glycoprotein (OMG) and some molecules involved in glutamatergic synapse maturation, such as receptors tyrosine kinases (TRKs), postsynaptic density (PSD-95) and N-methyl-D-aspartate receptors 2 A/B (NMDA2A/B). After treatment with the neurotoxicant trimethyltin (TMT), differentiated M3GFP-BDNF exhibit an attenuation of cellular damage which correlates with a significant activation of MAPK and PI3K/Akt signaling and delayed activation of death signals, while on M3GFP, TMT induces a significant reduction of cell survival, neuronal differentiation and concomitant earlier activation of cleaved caspase-3. We demonstrate that overexpression of BDNF firmly regulate cell survival and differentiation of NSC and protects differentiated NSC against TMT-induced neurotoxicity through the PI3K/Akt and MAPK signaling pathways.

UR - http://www.scopus.com/inward/record.url?scp=77954600512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954600512&partnerID=8YFLogxK

U2 - 10.1002/jcp.22170

DO - 10.1002/jcp.22170

M3 - Article

VL - 224

SP - 710

EP - 721

JO - Journal of cellular and comparative physiology

JF - Journal of cellular and comparative physiology

SN - 0021-9541

IS - 3

ER -