Modulation of the Core Neural Network in Stress: The Role of Brain-Derived Neurotrophic Factor and LTP

Abstract

The rat BDNF gene consists of 4 short 50 exons and a 30 exon encoding the mature BDNF protein (Timmusk et al. 1993). Quantitative PCR analysis of BDNF mRNA containing these five upstream exons indicates that each of the alternative transcripts is most abundant in the hippocampus, intermediate in the substantia nigra and cerebellum and least abundant in the striatum, although the magnitude of these differences in expression varies indicating that BDNF gene transcription in the mature brain is regulated by alternate promoters that are differentially active across these regions (Bishop et al. 1994). Thus the BDNF gene possesses differential exon regulation and usage with different subcellular distributions as well as different distributions in different parts of the brain. The gene consists of 8 untranslated 50 exons each possessing their own promoters with the possibility of being connected to a 30 coding exon, thus forming a tripartite transcript that allows for different splice variants of BDNF mRNA. So the rodent BDNF transcripts consist of a protein-coding exon spliced to one of eight noncoding exons as well as a transcript containing only the protein-coding exon. This structure of the rodent BDNF gene is shown in Fig. 4.1 [see Fig. 3 in Boulle et al. (2012)]. Exons are represented in this figure as boxes and the introns as lines with the exon numbers indicated in Roman numerals. The 30 coding exon (exon IX) contains two polyadenylation sites (poly A). The red box shows the region of exon IX coding for the pro-BDNF protein. It is the variety of transcripts made possible by this arrangement of the BDNF gene that allows for specificity to different regions of the brain (Aid et al. 2007). Furthermore, these transcripts of BDNF genes in rodents are not only specific to different regions of the cortex and archicortex, but their expression in these regions is under control of the epigenetic processes of histone deacetylation and DNA methylation. The flexibility provided by different splice variants of BDNF mRNA, with differences in their 50 or 30 extremities, together with epigenetic modulation of transcription of the BDNF gene, provides for a wide variety of regulatory processes in determining the formation and regression of dendritic spines in different brain regions in response to stress.

Reprinted from Prog. Neurobiol. Bennett MR and Lagopoulos J. Stress and trauma: BDNF control of dendritic-spine formation and regression. Vol. 112:80–99. Copyright (2014). With permission from Elsevier.