Elsevier

Neuroscience

Volume 88, Issue 4, February 1999, Pages 1009-1014
Neuroscience

Letter to Neuroscience
Brain-derived neurotrophic factor regulates the expression of AMPA receptor proteins in neocortical neurons

https://doi.org/10.1016/S0306-4522(98)00496-5Get rights and content

Abstract

The role of the neurotrophins; nerve growth factor,[22]brain-derived neurotrophic factor,[2]neurotrophin-316, 24and neurotrophin-4/5,[3]in synaptic development and plasticity has been extensively investigated.23, 33The neurotrophins regulate synaptic transmission1, 13, 19, 34as well as neural development4, 5, 12, 18, 25in the brain. However, the mechanisms underlying these processes are unknown. In this study we show that brain-derived neurotrophic factor triggers an increase in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor (GluR) proteins without significant changes in their messenger RNA levels. Brain-derived neurotrophic factor treatment specifically increased the protein levels of GluR1 (193±22%) and GluR2/3 (182±11%) in cultured rat neocortical neurons. In contrast, nerve growth factor and neurotrophin-3 failed to alter the protein levels of these neurons, and brain-derived neurotrophic factor effects on N-methyl-D-aspartate-type glutamate receptors were either modest or negligible. Immunocytochemical studies indicated that the increase in AMPA receptor proteins reflects the induction of their neuronal expression, but not selective neuronal survival. In agreement with these results, cortical neurons from brain-derived neurotrophic factor-knockout mice exhibited a reduction in AMPA receptor proteins in the cytoskeletal fraction containing postsynaptic proteins.

Thus, the neurotrophin plays a crucial role in modulating the expression of AMPA receptors presumably at translational or post-translation levels and is implicated in synaptic development and plasticity.

Section snippets

Discussion

In the present study, our results suggest that BDNF can increase specifically protein levels of AMPA receptors. Reversibly, expression of BDNF itself is known to be induced by activation of AMPA receptors in the brain.11, 35Therefore, these two observations indicate that BDNF and AMPA receptors mutually interact with each other to regulate positively the other expression. Their interactions might contribute to normal brain development and plasticity.23, 33

The receptor increase appeared to occur

Acknowledgements

We thank Dr P. Ernfors and Dr R. Jaenisch for providing the brain tissues from BDNF mutant mice, Miss J. H. Kogan and Mrs C. Fujikawa for technical assistance, Dr S. Heinemann for rat GluR1 cDNA, Dr K. Sakimura for mouse GluR2 cDNA and GluR2/3 antibodies, and Dr T. Yamamoto for his advice. This project was supported by the Japan Society for the Promotion of Science (RFTF-96L00203).

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