Brain-derived neurotrophic factor promotes the survival of neurons arising from the adult rat forebrain subependymal zone.
Neuronal precursor cells persist in the adult forebrain ependymal/subependymal zone (SZ) and have been found to produce neurons in cultures derived from birds, rodents, and humans. We postulated that the survival of neurons generated from these cells might be constrained in adulthood by the local absence of trophic support. To test this hypothesis, we established explant cultures of adult rat forebrain SZ and assessed the effect of defined neurotrophins on the survival of new neurons arising from these explants. We found that microtubule-associated protein 2+ neurons arose from explants derived from a wide area of the SZ, spanning the rostral 6 mm of the ventricular system. In cultures exposed to brain-derived neurotrophic factor (BDNF), > 35% of new neurons survived at 22 days in vitro (DIV), and > 25% survived at 42 DIV, concurrent with the virtually complete loss of neurons in unsupplemented controls. The surviving cells expressed trkB, the high-affinity receptor for BDNF. In contrast, neither nerve growth factor nor neurotrophic factor 3 enhanced neuronal survival. Thus, BDNF supports the survival of neurons produced by the adult rat forebrain and may act as a permissive factor for neuronal recruitment in adulthood.
Kirschenbaum
B
B
Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.
Goldman
S A
SA
D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002455:Cell Division / Q000187:drug effects; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D020933:Neurotrophin 3; D009924:Organ Culture Techniques; D016548:Prosencephalon / Q000033:anatomy & histology / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D014316:Tritium; D013936:Thymidine