The Overview of BDNF Gene

BDNF is a member of the growth factor family, which is involved in promoting synaptic efficacy, neuronal connectivity and neuroplasticity. The BDNF protein is coded by the gene that is also called BDNF. It is has been verified that BDNF gene has an extremely complex genomic structure. In humans, BDNF gene is located on chromosome 11. BDNF gene in human presents eleven exons and nine functional promoters, producing up to seventeen different transcripts which encode for the same protein. On The Contrast, BDNF gene in rat has nine exons with its own promoter, producing nine different transcripts. BDNF gene with such a complex set of genomic promoters is thought to mediate accurate control of BDNF production. A plenty of evidence indicates that these different transcripts are distributed across brain regions in different cell types and even within different parts of the neuron. Exon III transcripts of rat BDNF gene are detected only in cell bodies, while IV transcripts are found in cell bodies and dendritic processes of visual cortex neurons. These promoters are differentially activated in response to diverse and varied signaling events, including epigenetic regulation.

A single nucleotide polymorphism in the BDNF gene, substitution of a valine for a methionine at the codon 66 (val66met), is involved in altered trafficking of BDNF. Such change seems to take place due to a reduced interaction of BDNF and sortilin inducing metBDNF aggregation to the cell body of neurons and thus preventing it to interact with synaptophysin. That would in turn reduce the BDNF secretion into the synapse. Further, knock-in BDNF met/met mice have abnormal dendritic arborization in the dentate gyrus and display anxious-related behaviors that are not normalized by antidepressant treatment. In BD patients, the val66met substitution in the BDNF gene has been associated with impaired cognitive performance, and suicidal behavior.