Fibroblast growth factor-2/brain-derived neurotrophic factor-associated maturation of new neurons generated from adult human subependymal cells

David W. Pincus, H. Michael Keyoung, Catherine Harrison-Restelli, Robert R. Goodman, Richard A.R. Fraser, Mark Edgar, Shin Ichi Sakakibara, Hideyuki Okano, Maiken Nedergaard, Steven A. Goldman

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Abstract

The adult mammalian forebrain harbors neuronal precursor cells in the subependymal zone (SZ). Neuronal progenitors also persist in the adult human SZ and have been cultured from epileptic temporal lobe. In the present study, we sought to identify these neural progenitors in situ, and to direct their expansion and neuronal differentiation in vitro. We prepared explants of adult human SZ, obtained from temporal lobe resections of refractory epileptics. The resultant cultures were treated with fibroblast growth factor-2 (FGF-2) for a week, with concurrent exposure to [3H]thymidine, then switched to media containing brain-derived neurotrophic factor (BDNF) for up to 2 months. Sporadic neuronal outgrowth, verified antigenically and physiologically, was observed from SZ cultures regardless of FGF-2/BDNF treatment; however, only FGF-2/BDNF-treated cultures exhibited profuse outgrowth, and these displayed neuronal survival as long as 9 weeks in vitro. In addition, cortical cultures derived from two brains generated microtubule- associated protein-2+ neurons, which incorporated [3H]thymidine and exhibited significant calcium increments to depolarization. In histological sections of the subependyma, both uncommitted and restricted progenitors, defined respectively by musashi and Hu protein expression, were identified. Thus, the adult human subependyma harbors neural progenitors, which are able to give rise to neurons whose numbers can be supported for prolonged periods in vitro.

Original languageEnglish
Pages (from-to)576-585
Number of pages10
JournalAnnals of Neurology
Volume43
Issue number5
DOIs
Publication statusPublished - 1998 May 1

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ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Pincus, D. W., Keyoung, H. M., Harrison-Restelli, C., Goodman, R. R., Fraser, R. A. R., Edgar, M., Sakakibara, S. I., Okano, H., Nedergaard, M., & Goldman, S. A. (1998). Fibroblast growth factor-2/brain-derived neurotrophic factor-associated maturation of new neurons generated from adult human subependymal cells. Annals of Neurology, 43(5), 576-585. https://doi.org/10.1002/ana.410430505