PMID- 25059794 OWN - NLM STAT- MEDLINE DCOM- 20150916 LR - 20220309 IS - 1932-846X (Electronic) IS - 1932-8451 (Print) IS - 1932-8451 (Linking) VI - 75 IP - 2 DP - 2015 Feb TI - Withdrawal of BDNF from hippocampal cultures leads to changes in genes involved in synaptic function. PG - 173-92 LID - 10.1002/dneu.22216 [doi] AB - Neurotrophins play a crucial role in mediating neuronal survival and synaptic plasticity. A lack of trophic factor support in the peripheral nervous system (PNS) is associated with a transcription-dependent programmed cell death process in developing sympathetic neurons. While most of the attention has been on events culminating in cell death in the PNS, the earliest events that occur after trophic factor withdrawal in the central nervous system (CNS) have not been investigated. In the CNS, brain-derived neurotrophic factor (BDNF) is widely expressed and is released in an activity-dependent manner to shape the structure and function of neuronal populations. Reduced neurotrophic factor support has been proposed as a mechanism to account for changes in synaptic plasticity during neurodevelopment to aging and neurodegenerative disorders. To this end, we performed transcriptional profiling in cultured rat hippocampal neurons. We used a TrkB ligand scavenger (TrkB-FC ) to sequester endogenous neurotrophic factor activity from hippocampal neurons in culture. Using a high-density microarray platform, we identified a significant decrease in genes that are associated with vesicular trafficking and synaptic function, as well as selective increases in MAP kinase phosphatases. A comparison of these changes with recent studies of Alzheimer's disease and cognitive impairment in postmortem brain tissue revealed striking similarities in gene expression changes for genes involved in synaptic function. These changes are relevant to a wide number of conditions in which levels of BDNF are compromised. CI - (c) 2014 Wiley Periodicals, Inc. FAU - Mariga, Abigail AU - Mariga A AD - Cell and Molecular Biology Program, New York University Langone Medical Center, New York, New York, 10016. FAU - Zavadil, Jiri AU - Zavadil J FAU - Ginsberg, Stephen D AU - Ginsberg SD FAU - Chao, Moses V AU - Chao MV LA - eng GR - P30 CA016087/CA/NCI NIH HHS/United States GR - NS21072/NS/NINDS NIH HHS/United States GR - AG025970/AG/NIA NIH HHS/United States GR - P01 AG014449/AG/NIA NIH HHS/United States GR - AG043375/AG/NIA NIH HHS/United States GR - R01 AG025970/AG/NIA NIH HHS/United States GR - P01 AG017617/AG/NIA NIH HHS/United States GR - R56 NS021072/NS/NINDS NIH HHS/United States GR - AG014449/AG/NIA NIH HHS/United States GR - AG017617/AG/NIA NIH HHS/United States GR - R01 AG043375/AG/NIA NIH HHS/United States GR - R01 NS021072/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 - 20140825 PL - United States TA - Dev Neurobiol JT - Developmental neurobiology JID - 101300215 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Central Nervous System Agents) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.1.3.16 (Mitogen-Activated Protein Kinase Phosphatases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*deficiency MH - Cells, Cultured MH - Central Nervous System Agents/pharmacology MH - Gene Expression Profiling MH - Gene Expression Regulation/physiology MH - Hippocampus/drug effects/*physiology MH - Microarray Analysis MH - Mitogen-Activated Protein Kinase Phosphatases/genetics/metabolism MH - Neuronal Plasticity/drug effects/genetics/*physiology MH - Neurons/drug effects/*physiology MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Receptor, trkB/agonists PMC - PMC4329925 MID - NIHMS660972 OTO - NOTNLM OT - BDNF deprivation OT - hippocampus OT - microarray OT - neurodegeneration OT - synaptic function OT - transcription EDAT- 2014/07/26 06:00 MHDA- 2015/09/17 06:00 PMCR- 2016/02/01 CRDT- 2014/07/26 06:00 PHST- 2014/01/14 00:00 [received] PHST- 2014/06/26 00:00 [revised] PHST- 2014/07/23 00:00 [accepted] PHST- 2014/07/26 06:00 [entrez] PHST- 2014/07/26 06:00 [pubmed] PHST- 2015/09/17 06:00 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - 10.1002/dneu.22216 [doi] PST - ppublish SO - Dev Neurobiol. 2015 Feb;75(2):173-92. doi: 10.1002/dneu.22216. Epub 2014 Aug 25.