Premium
Withdrawal of BDNF from hippocampal cultures leads to changes in genes involved in synaptic function
Author(s) -
Mariga Abigail,
Zavadil Jiri,
Ginsberg Stephen D.,
Chao Moses V.
Publication year - 2015
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.22216
Subject(s) - tropomyosin receptor kinase b , neurotrophic factors , biology , neurotrophin , neuroscience , synaptic plasticity , hippocampal formation , brain derived neurotrophic factor , synaptic fatigue , neuroplasticity , receptor , genetics
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‐F C ) 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. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 173–192, 2015