Mouse and rat BDNF gene structure and expression revisited

Abstract

Brain-derived neurotrophic factor (BDNF) has important functions in the development of the nervous system and in brain plasticity-related processes such as memory, learning, and drug addiction. Despite the fact that the function and regulation of rodent BDNF gene expression have received close attention during the last decade, knowledge of the structural organization of mouse and rat BDNF gene has remained incomplete. We have identified and characterized several mouse and rat BDNF transcripts containing novel 5 0 untranslated exons and introduced a new numbering system for mouse and rat BDNF exons. According to our results both mouse and rat BDNF gene consist of eight 5 0 untranslated exons and one protein coding 3 0 exon. Transcription of the gene results in BDNF transcripts containing one of the eight 5 0 exons spliced to the protein coding exon and in a transcript containing only 5 0 extended protein coding exon. We also report the distinct tissue-specific expression profiles of each of the mouse and rat 5 0 exon-specific transcripts in different brain regions and nonneural tissues. In addition, we show that kainic acid-induced seizures that lead to changes in cellular Ca 2+ levels as well as inhibition of DNA methylation and histone deacetylation contribute to the differential regulation of the expression of BDNF transcripts. Finally, we confirm that mouse and rat BDNF gene loci do not encode antisense mRNA transcripts, suggesting that mechanisms of regulation for rodent and human BDNF genes differ substantially. V V C 2006 Wiley-Liss, Inc.

The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons

“…11 The genomic structure of BDNF in rodents is complex, containing multiple 5 0 -untranslated exons and one protein-coding 3 0 exon. [12][13][14] Each of these untranslated exons is alternatively spliced to produce various BDNF mRNA species. Initially, only four untranslated exons were found to be in the rat BDNF gene.…”

“…Initially, only four untranslated exons were found to be in the rat BDNF gene. 12 More recent studies show that eight untranslated exons are present in the rodent (mouse and rat) BDNF gene 13,14 and thus these promoters have been renamed. Accordingly, former rat exon III, exon IV and exon V are now termed exon IV, VI and IX, respectively.…”

“…14 These rodent BDNF-splicing variants display distinct expression profiles in the brain regions and show differential regulation following treatment of rats with cocaine 13 or kainic acid. 14 Exon IV (formerly rat exon III 12 )-containing transcripts of BDNF are robustly expressed in response to KClinduced membrane depolarization in primary cultures of rat cortical neurons. 15 This transcriptional activation requires the promoter region 80 bp upstream from the transcription initiation site of exon IV-containing three calcium-responsive elements, CaRE1, CaRE2 and CaRE3/CRE, to which their respective stimulating factors, CaRF, USF1/2 and cyclicAMP responsive element binding protein (CREB), are bound.…”

Epigenetic Regulation of BDNF Expression via the Scaffolding Protein RACK1

“…BDNF plays an important role in neuronal proliferation, differentiation, and survival, as well as synaptic plasticity, learning, and memory (23,25,26). The genomic structure of the BDNF gene consists of eight 5Ј-non-coding exons and one 3Ј-coding exon (27,28) and is very similar between human and rodents (27)(28)(29)(30). The expression of each of the eight 5Ј exons is separately controlled by an individual promoter, which is then spliced to the common 3Ј exon that encodes the BDNF protein (28,31).…”

The exclusive induction of extinction is gated by BDNF

“…Hybridizations were performed essentially as described by Hall et al (2001a). cDNA antisense probes (45-mers) were synthesized commercially (SigmaGenosys) complementary to nucleotides 3 -47 of Zif268 (NM 012551, 5 ′ -CCGTTGCTCAG-CAGCATCATCTCCTCCAGTTTGGGGTAGTTGTCC) and nucleotides 855-899 of protein-encoding BDNF exon IX (Liu et al 2005;Aid et al 2007) (NM 012513.3, 5 ′ -CGAAC-CTTCTGG-TCCTCATCCAGCAGCTCTTCGA-TCACGTGCTCA). These oligonucleotides were 3 ′ -end labeled with [a-35 S] dATP (1200 Ci/ mmol; Perkin Elmer-NEN) in a 30:1 molar ratio of radiolabeled ATP:oligonucleotide using terminal deoxynucleotidyl transferase (Promega) as described previously (Wisden and Morris 1994).…”