Fibroblast growth factor-2/brain-derived neurotrophic factor-associated maturation of new neurons generated from adult human subependymal cells.
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.
Pincus
D W
DW
Department of Neurosurgery, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Keyoung
H M
HM
Harrison-Restelli
C
C
Goodman
R R
RR
Fraser
R A
RA
Edgar
M
M
Sakakibara
S
S
Okano
H
H
Nedergaard
M
M
Goldman
S A
SA
D000328:Adult; D000367:Age Factors; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size; D002478:Cells, Cultured; D002648:Child; D029721:Drosophila Proteins; D051959:ELAV Proteins; D004558:Electric Stimulation; D004805:Ependyma / Q000737:chemistry / Q000166:cytology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000032:analysis; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D029721:Drosophila Proteins; D051959:ELAV Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C088623:msi protein, Drosophila; D016222:Fibroblast Growth Factor 2; D002118:Calcium