1. ¹Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
2. ²Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3. ³Department of Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4. ⁴Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA

Correspondence: Dr K Mirnics, Department of Psychiatry, University of Pittsburgh School of Medicine, E1655 Biomed Sci Tower, Pittsburgh, PA 15261, USA. E-mail: karoly+@pitt.edu

Received 31 January 2006; Revised 13 March 2006; Accepted 24 March 2006; Published online 9 May 2006.

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.