Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood.
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.
Glorioso
C
C
Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15261, USA.
Sabatini
M
M
Unger
T
T
Hashimoto
T
T
Monteggia
L M
LM
Lewis
D A
DA
Mirnics
K
K
D000818:Animals; D001927:Brain Diseases / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003433:Crosses, Genetic; D004318:Doxycycline / Q000494:pharmacology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D017781:Genes, Immediate-Early; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D007395:Interneurons / Q000737:chemistry / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000145:classification / Q000378:metabolism; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010641:Phenotype; D017397:Prefrontal Cortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D017384:Sequence Deletion; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic; D005680:gamma-Aminobutyric Acid / Q000032:analysis
D019208:Brain-Derived Neurotrophic Factor; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D011993:Recombinant Fusion Proteins; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D004318:Doxycycline