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


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
Issue number3
Publication statusPublished - Sep 2010

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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