Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family shown initially to influence the differentiation and survival of neurons (Barde et al, 1982) and subsequently established to mediate in the central nervous system (CNS) higher order activities, such as synaptic plasticity, and learning and memory (Park and Poo, 2013). BDNF is widely expressed throughout the CNS, and in response to neuronal depolarization, BDNF is secreted into the synapse leading to the activation of tropomyosin receptor kinase B and its downstream signaling cascades that contribute to gene transcriptional events critical for synaptic plasticity and cognitive function. Interestingly, among the growth factors in the CNS, BDNF is one of the few that has its own expression regulated by neuronal activity.

BDNF expression, both in rodents and in humans, is under tight control by nine distinct promoters, as well as two 3′ UTR polyadenylation sites. The entire coding sequence is in exon 9 and each of the eight upstream exons is spliced to exon 9 (West et al, 2014). Combinatorial use of multiple promoters and polyadenylation sites generate at least 18 distinct BDNF transcripts; however, these different BDNF transcripts ultimately lead to translation of the same BDNF protein. This high level of transcriptional regulation has been postulated to generate a putative ‘code’ that allows for exquisite spatiotemporal and stimuli-dependent regulation of BDNF expression within different subdomains of the neurons, as well as in different brain regions.

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