PMID- 11304717 OWN - NLM STAT- MEDLINE DCOM- 20010628 LR - 20190906 IS - 0021-9967 (Print) IS - 0021-9967 (Linking) VI - 433 IP - 4 DP - 2001 May 14 TI - Target-derived BDNF (brain-derived neurotrophic factor) is essential for the survival of developing neurons in the isthmo-optic nucleus. PG - 550-64 AB - Neurons in the peripheral nervous system depend on single neurotrophic factors, whereas those in the brain are thought to utilize many different trophic factors. This study examined whether some neurons in the brain critically depend on a single trophic factor during development. Neurons in the isthmo-optic nucleus (ION) of chick embryos respond to exogenous brain-derived neurotrophic factor (BDNF). Relatively high concentrations of endogenous BDNF were present in the ION of 14-18-day-old chick embryos. ION target cells in the retina were immunolabeled for BDNF but showed surprisingly low levels of BDNF mRNA. These data suggest that ION target cells derive some BDNF from other retinal sources. No BDNF mRNA was detected in the ION itself. ION neurons had a very efficient retrograde transport system for BDNF and exogenous BDNF arrived in the ION intact. When the ION was deprived of endogenous trkB ligands by injection of trkB fusion proteins in the eye, cell death of ION neurons was enhanced, and this effect was mimicked by BDNF-specific blocking antibodies in the eye. TrkB fusion proteins in the retina induced cell death of ION neurons prior to visible effects on ION target cells in the retina. Immunolabel for endogenous BDNF was sparse in pyknotic ION neurons, suggesting that ION neurons with low BDNF content were eliminated by apoptosis. These data show that BDNF is an essential target-derived trophic factor for developing ION neurons and thereby validate the neurotrophic hypothesis for at least one neuronal population in the brain. CI - Copyright 2001 Wiley-Liss, Inc. FAU - Von Bartheld, C S AU - Von Bartheld CS AD - Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA. chrisvb@physio.unr.edu FAU - Johnson, J E AU - Johnson JE LA - eng GR - EY 11127/EY/NEI NIH HHS/United States GR - NS 35931/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Comp Neurol JT - The Journal of comparative neurology JID - 0406041 RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (RNA, Messenger) RN - EC 1.6.99.1 (NADPH Dehydrogenase) RN - EC 2.7.10.1 (Receptor, trkB) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Animals MH - Antibodies/pharmacology MH - Brain/cytology/*embryology/metabolism MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism/pharmacology MH - Cell Communication/drug effects/physiology MH - Cell Death/drug effects/physiology MH - Cell Differentiation/drug effects/*physiology MH - Cell Survival/drug effects/*physiology MH - Chick Embryo/cytology/*embryology/metabolism MH - Immunohistochemistry MH - NADPH Dehydrogenase/metabolism MH - Nerve Growth Factors/metabolism/pharmacology MH - Neurons/cytology/drug effects/*metabolism MH - RNA, Messenger/metabolism MH - Receptor, trkB/metabolism MH - Retina/cytology/embryology/metabolism MH - Visual Pathways/cytology/*embryology/metabolism EDAT- 2001/04/17 10:00 MHDA- 2001/06/29 10:01 CRDT- 2001/04/17 10:00 PHST- 2001/04/17 10:00 [pubmed] PHST- 2001/06/29 10:01 [medline] PHST- 2001/04/17 10:00 [entrez] AID - 10.1002/cne.1159 [doi] PST - ppublish SO - J Comp Neurol. 2001 May 14;433(4):550-64. doi: 10.1002/cne.1159.