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The 3' UTRs of Brain-Derived Neurotrophic Factor Transcripts Differentially Regulate the Dendritic Arbor
Kate M O'Neill1,2, Katherine E Donohue1, Anton Omelchenko1,3
1Department of Cell Biology and Neuroscience, Rutgers University, The State University of New Jersey, Piscataway, NJ, United States.
Frontiers in Cellular Neuroscience
|March 23, 2018
Summary
Intracellular brain-derived neurotrophic factor (BDNF) mRNA localization impacts neuronal dendrite growth. Specific mRNA variants alter dendritic branching, mediated by the TrkB receptor, highlighting the role of mRNA transport in dendrite patterning.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Dendrite patterning is crucial for neuronal function and is influenced by factors like brain-derived neurotrophic factor (BDNF).
- Previous studies showed extracellular BDNF affects dendritic arbors differently based on application method.
- Intracellular BDNF localization is key to understanding its role in dendritogenesis.
Purpose of the Study:
- To investigate how intracellular overexpression of BDNF mRNA variants affects dendrite development in hippocampal neurons.
- To determine if the 3' untranslated regions (UTRs) of BDNF mRNA influence its targeting and subsequent effects on dendrites.
- To examine the role of the BDNF receptor, TrkB, in mediating these changes.
Main Methods:
- Overexpression of different BDNF mRNA variants (with or without 3' UTRs) in hippocampal neurons.
- Analysis of dendritic branching patterns using Sholl distribution curves.
- Inhibition of the TrkB receptor to assess its role in mediating BDNF effects.
- Examination of a non-natural BDNF mRNA variant with a specific 3' UTR portion.
Main Results:
- Overexpression of BDNF mRNA variants significantly altered dendritic branching compared to controls.
- Both shorter and longer BDNF mRNA variants induced similar changes in Sholl curves, contrary to expected localization differences.
- TrkB inhibition blocked increases in Sholl curves, with effects varying based on the mRNA's 3' UTR.
- Overexpression of a specific 3' UTR portion increased branching near the cell body, dependent on TrkB activity.
Conclusions:
- The spatial localization of BDNF mRNA, dictated by its 3' UTRs, influences local dendrite growth.
- TrkB receptor activity is essential for mediating BDNF-induced changes in dendrite morphology.
- Intracellular transport and localization of BDNF mRNA play a critical role in regulating dendrite patterning.