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Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood

Molecular Psychiatry volume 11, pages 633–648 (2006)Cite this article

Abstract

Brain-derived neurotrophic factor (BDNF) has been reported to be critical for the development of cortical inhibitory neurons. However, the effect of BDNF on the expression of transcripts whose protein products are involved in gamma amino butric acid (GABA) neurotransmission has not been assessed. In this study, gene expression profiling using oligonucleotide microarrays was performed in prefrontal cortical tissue from mice with inducible deletions of BDNF. Both embryonic and adulthood ablation of BDNF gave rise to many shared transcriptome changes. BDNF appeared to be required to maintain gene expression in the SST-NPY-TAC1 subclass of GABA neurons, although the absence of BDNF did not alter their general phenotype as inhibitory neurons. Furthermore, we observed expression alterations in genes encoding early-immediate genes (ARC, EGR1, EGR2, FOS, DUSP1, DUSP6) and critical cellular signaling systems (CDKN1c, CCND2, CAMK1g, RGS4). These BDNF-dependent gene expression changes may illuminate the biological basis for transcriptome changes observed in certain human brain disorders.

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Acknowledgements

We are thankful to Drs Pat R Levitt and Etienne Sibille for valuable comments on the manuscript. We also thank for Dr Dominique Arion, Katherine C Douglass, Annie Bedison and Melissa Macioce for superb technical assistance with the experiments. This work was supported by R01 MH067234 (KM), 2 P50 MH45156-14 CCNMD Project 2 (KM) and K02 MH070786 (KM).

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  1. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    C Glorioso, M Sabatini, T Unger, T Hashimoto, D A Lewis & K Mirnics

  2. Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    M Sabatini & K Mirnics

  3. Department of Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    D A Lewis

  4. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA

    L M Monteggia

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Correspondence to K Mirnics.

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Glorioso, C., Sabatini, M., Unger, T. et al. Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood. Mol Psychiatry 11, 633–648 (2006). https://doi.org/10.1038/sj.mp.4001835

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  • DOI: https://doi.org/10.1038/sj.mp.4001835

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