PMID- 19409492 OWN - NLM STAT- MEDLINE DCOM- 20090907 LR - 20211020 IS - 1095-9327 (Electronic) IS - 1044-7431 (Print) IS - 1044-7431 (Linking) VI - 41 IP - 4 DP - 2009 Aug TI - Brain-derived neurotrophic factor regulates early postnatal developmental cell death of dopamine neurons of the substantia nigra in vivo. PG - 440-7 LID - 10.1016/j.mcn.2009.04.009 [doi] AB - Brain-derived neurotrophic factor (BDNF) was the first purified molecule identified to directly support the development of mesencephalic dopamine neurons. However, its physiologic role has remained unknown. Based on patterns of expression, it is unlikely to serve as a target-derived neurotrophic factor, but it may instead act locally in the mesencephalon, either released by afferent projections, or in autocrine fashion. To assess a possible local role, we blocked BDNF signaling in the substantia nigra (SN) of postnatal rats by injection of either neutralizing antibodies or a peptide antagonist. These treatments increased the magnitude of developmental cell death in the SN, indicating that endogenous local BDNF does play a regulatory role. However, we also find that elimination of BDNF in brain throughout postnatal development in BDNF(fl/fl):Nestin-Cre mice has no effect on the adult number of SN dopamine neurons. We postulate that other forms of trophic support may compensate for the elimination of BDNF during early development. Although the number of SN dopamine neurons is unchanged, their organization is disrupted. We conclude that BDNF plays a physiologic role in the postnatal development of SN dopamine neurons. FAU - Oo, Tinmarla F AU - Oo TF AD - Department of Neurology, The College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. FAU - Marchionini, Deanna M AU - Marchionini DM FAU - Yarygina, Olga AU - Yarygina O FAU - O'Leary, Paul D AU - O'Leary PD FAU - Hughes, Richard A AU - Hughes RA FAU - Kholodilov, Nikolai AU - Kholodilov N FAU - Burke, Robert E AU - Burke RE LA - eng GR - R56 NS026836/NS/NINDS NIH HHS/United States GR - P50 NS038370/NS/NINDS NIH HHS/United States GR - NS38370/NS/NINDS NIH HHS/United States GR - R01 NS026836-19/NS/NINDS NIH HHS/United States GR - R01 NS026836/NS/NINDS NIH HHS/United States GR - P50 NS038370-100003/NS/NINDS NIH HHS/United States GR - NS26836/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090503 PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Antibodies) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Intermediate Filament Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nes protein, mouse) RN - 0 (Nes protein, rat) RN - 0 (Nestin) RN - 0 (Peptides) RN - 0 (RNA, Messenger) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Age Factors MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Antibodies/pharmacology MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/genetics/immunology/*metabolism MH - Cell Death/physiology MH - Dopamine/*metabolism MH - Female MH - Gene Expression Regulation, Developmental/drug effects/*genetics MH - In Situ Nick-End Labeling/methods MH - Intermediate Filament Proteins/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Nerve Tissue Proteins/genetics MH - Nestin MH - Neurons/drug effects/*physiology MH - Peptides/pharmacology MH - Pregnancy MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Substantia Nigra/*cytology/*growth & development MH - Tyrosine 3-Monooxygenase/metabolism PMC - PMC2743455 MID - NIHMS114711 EDAT- 2009/05/05 09:00 MHDA- 2009/09/08 06:00 PMCR- 2010/08/01 CRDT- 2009/05/05 09:00 PHST- 2008/12/05 00:00 [received] PHST- 2009/03/25 00:00 [revised] PHST- 2009/04/22 00:00 [accepted] PHST- 2009/05/05 09:00 [entrez] PHST- 2009/05/05 09:00 [pubmed] PHST- 2009/09/08 06:00 [medline] PHST- 2010/08/01 00:00 [pmc-release] AID - S1044-7431(09)00088-8 [pii] AID - 10.1016/j.mcn.2009.04.009 [doi] PST - ppublish SO - Mol Cell Neurosci. 2009 Aug;41(4):440-7. doi: 10.1016/j.mcn.2009.04.009. Epub 2009 May 3.