Featured Finding Figure
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 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. For example, two-way clustering of the normalized expression levels for 31 genes revealed common expression changes in embryonic and adult BDNF-ablated mice (left side of figure). Columns represent individual animals (purple-cKO; blue-wild-type control) and rows denote individual genes. Each colored pixel denotes log2-normalized expression levels in a single animal. The intensity of red pixels is proportional to the increase in transcript expression, whereas green pixel intensity is proportional to the decrease in transcript expression. Note that the clustering is identical in the two groups of the BDNF-deficient animals. Furthermore, normal BDNF levels are required for maintenance of early-immediate genes (IEG), somatostatin (SST), tachikinin 1 (TAC1) and neuropeptide Y (NPY) expression, but not parvalbumin (PV) or glutamic acid decarboxylase 1 (GAD67) (left panel). Thus, BDNF appears to be required to maintain gene expression in the SST-NPY-TAC1 subclass of GABA neurons, although the absence of BDNF does not alter their general phenotype as inhibitory neurons.
Glorioso C, Sabatini M, Unger T, Hashimoto T, Monteggia LM, Lewis DA and Mirnics K, Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood. Molecular Psychiatry 11: 366-648, 2006.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
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