Research report
Distinctive four promoters collectively direct expression of brain-derived neurotrophic factor gene

https://doi.org/10.1016/0169-328X(94)90251-8Get rights and content

Abstract

In order to get a deeper insight into comprehensive understanding of gene regulation of brain-derived neurotrophic factor (BDNF), we characterized the transcriptional apparatus of this gene on the basis of the genomic structure. The results in this study revealed that there are at least four distinctive promoters in the BDNF gene; two of them are neuron-specific and the rest are active in some non-neuronal tissues as well as neuronal ones. Although the analyses of the promoter usage pattern clarified many characteristic features in controlling these promoter activities, the most notable finding was that administration of kainic acid resulted in great activation of two out of the four promoters in hippocampal neurons in a regionally different manner and thus indicated the presence of two distinct signal transduction pathways for kainate-induced activation of BDNF gene expression in neurons. The analysis of BDNF gene expression in terms of the promoter usage pattern would provide a new and important insight into understanding a molecular control mechanism of this gene expression.

References (30)

  • A. Shintani et al.

    Characterization of the 5′-flanking region of the human brain-derived neurotrophic factor

    Biochem. Biophys. Res. Commun.

    (1992)
  • M. Thompson et al.

    Structure of the gene encoding peripherin, an NGF-regulated neuronal-specific type III intermediate filament protein

    Neuron

    (1989)
  • T. Timmusk et al.

    Multiple promoters direct tissue-specific expression of the rat BDNF gene

    Neuron

    (1993)
  • L.M. Angerer et al.

    In situ hybridization with RNA probes: an annotated recipe

  • B. Christy et al.

    DNA binding site of the growth factor-inducible protein Zif268

  • Cited by (79)

    • Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity

      2015, Neuropharmacology
      Citation Excerpt :

      All of the transcripts are found in the hippocampus, though at different levels, and with different cellular and subcellular distributions (An et al., 2008; Kokaia et al., 1994; Timmusk et al., 1993). Their expression is differentially regulated by a variety of inputs including alterations in neuronal activity (Metsis et al., 1993; Nakayama et al., 1994; Timmusk et al., 1993), exercise (e.g. (Garcia et al., 2003; Oliff et al., 1998)), treatment with antidepressants (Russo-Neustadt et al., 2004), and various stress paradigms (reviewed in (Lauterborn et al., 1998)). Infusion of IL-1β into the hippocampus decreased its capacity for transcription of BDNF following learning (Barrientos et al., 2004), and infusion of IL-1ra protected it from the deleterious effects of IL-1β induced by a social isolation stress paradigm (Barrientos et al., 2003).

    • Involvement of brain-derived neurotrophic factor in late-life depression

      2013, American Journal of Geriatric Psychiatry
      Citation Excerpt :

      We further examined the molecular basis of decreased BDNF synthesis in response to CORT treatment. The rat bdnf gene contains four distinct promoters that are linked to four main transcript forms.100 Although the functions of each BDNF transcript are not clearly known, BDNF transcripts are differentially expressed across brain regions and are differentially regulated.101,102

    • Behavioral changes after maternal separation are reversed by chronic constant light treatment

      2012, Brain Research
      Citation Excerpt :

      Treatment with escitalopram did not change the maternal separation-induced increase in BDNF levels. The BDNF gene has four transcript forms, which facilitate regulation of BDNF expression on many levels (Nakayama et al., 1994; Timmusk et al., 1993). The various receptor subtypes of the endogenous opioid system have been found to differentially mediate behavioral mood states.

    View all citing articles on Scopus
    View full text