title: Withdrawal of BDNF from hippocampal cultures leads to changes in genes involved in synaptic function.
abstract: 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.
authors: Cell and Molecular Biology Program, New York University Langone Medical Center, New York, New York, 10016.
authors: Abigail
authors: A
authors: Mariga
authors: Jiri
authors: J
authors: Zavadil
authors: Stephen D
authors: SD
authors: Ginsberg
authors: Moses V
authors: MV
authors: Chao
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency*; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D046228:Microarray Analysis; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020813:Receptor, trkB / Q000819:agonists
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002491:Central Nervous System Agents; D020813:Receptor, trkB; D054639:Mitogen-Activated Protein Kinase Phosphatases
keywords: BDNF deprivation; hippocampus; microarray; neurodegeneration; synaptic function; transcription