Targeting novel integrative nuclear FGFR1 signaling by nanoparticle-mediated gene transfer stimulates neurogenesis in the adult brain

Integr Biol (Camb). 2009 Jun;1(5-6):394-403. doi: 10.1039/b902617g. Epub 2009 May 8.

Abstract

Neurogenesis, the process of differentiation of neuronal stem/progenitor cells (NS/PC) into mature neurons, holds the key to the treatment of various neurodegenerative disorders, which are a major health issue for the world's aging population. We report that targeting the novel integrative nuclear FGF Receptor 1 signaling (INFS) pathway enhances the latent potential of NS/PCs to undergo neuronal differentiation, thus promoting neurogenesis in the adult brain. Employing organically modified silica (ORMOSIL)-DNA nanoplexes to efficiently transfect recombinant nuclear forms of FGFR1 and its FGF-2 ligand into the brain subventricular zone, we find that INFS stimulates the NS/PC to withdraw from the cell cycle, differentiate into doublecortin expressing migratory neuroblasts and neurons that migrate to the olfactory bulb, subcortical brain regions and in the brain cortex. Thus, nanoparticle-mediated non-viral gene transfer may be used to induce selective differentiation of NS/PCs, providing a potentially significant impact on the treatment of a broad range of neurological disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology*
  • Brain / physiology*
  • Cells, Cultured
  • Drug Carriers / chemistry
  • Female
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Neurogenesis / physiology*
  • Neurons / cytology*
  • Neurons / physiology*
  • Receptor, Fibroblast Growth Factor, Type 1 / physiology*
  • Signal Transduction / physiology
  • Transfection / methods*

Substances

  • Drug Carriers
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1