BDNF by Charlotte and Andie

What is BDNF? 

BDNF (brain derived neurotrophic factor) is a gene found in humans. This gene also creates the protein BDNF.

BDNF is generally known for being related to learning, memory, anxiety, depression, and eating disorders.

Structural representation of BDNF protein

The BDNF Protein

The BDNF protein helps neurons survive in the central and peripheral nervous systems. It also helps new neurons and synapses grow and divide.

The BDNF protein is part of the neurotrophin family. In its original form, it takes the shape of a very tightly-associated dimer (pictured above). This dimeric form is a knot structure made of individual strands that are twisted around one another and linked by disulfide bonds. The BDNF protein takes the shape of other nerve growth factors like Neurotrophin-3 and Neurotrophin 4/5.  NGF and Neurotrophin-3 contain 50% of BDNF's amino acids.

At the Cellular Level

BDNF is in the endogenous ligands gene family. Endogenous ligands create specialized proteins that bind to receptors and tell cells to develop or keep working. If ligands are damaged or altered, cell function in these neurons could diminish. 

For cells that are able to respond to BDNF, BDNF binds to two receptors on the surface of a cell. These receptors are called TrkB, p75, and LNGFR. Scientists are currently unclear of the specific roles of these individual receptors.

Epigenetic Effects

Some treatments for low BDNF levels utilize epigenetics. The basic premise of epigenetics is the altering of genes through environmental factors.  So, epigenetics may explain why psychiatric disorders caused by BDNF are so hard to treat: BDNF has been coded to not signal properly.


Scientists have been working to develop drugs that can reverse epigenetic effects. These drugs aim to modify the BDNF signaling to erase the incorrect coding, and thereby cure the psychiatric disorder. Experimenting with rats that have conditions like "socially defeated" and "cocaine addict," scientists alter specific exons, which in turn affect specific parts of the brain and corresponding BDNF. This can help cure the epigenetic effects of BDNF that cause psychiatric disorders.

Changing BDNF Levels With Depression Treatment

Discovery

The nerve growth factor (NGF) was discovered in the 1950s. NGFs help neurons grow and survive. The discovery of the NGF led to the discovery of the closely related BDNF protein, which is actually a specific protein in the NGF family. BDNF was the second type of NGF to be discovered.

Medical Implications of the Discovery of BDNF

The first condition BDNF is related to is learning. BDNF works in the areas associated with learning and complex thought processes, including the hippocampus, cerebral cortex, and basal forebrain. BDNF is also very important to long-term memory.

The second condition BDNF is related to is WAGRO syndrome, which occurs when chromosome 11 (BDNF’s chromosome) is erased. WARGO syndrome can cause tumors, retardation, and other abnormal symptoms. WARGO is not a result of a missing BDNF gene, but a result of the whole chromosome missing.

Some other common mutations of the BDNF gene are linked to the development of psychiatric disorders (bipolar disorder, schizophrenia, anxiety, depression and eating disorders). These psychiatric disorders are likely caused by a change in one amino acid in the BDNF protein, which prohibits it from functioning. In a study done on 1,300 subjects with eating disorders, a specific MET66 variation of the BDNF gene appeared in most subjects. It is also likely that environmental factors can alter levels of BDNF and cause psychiatric disorders.

When a person has major depressive disorder and is depressed for at least 2 weeks (along with many other symptoms), NGFs like BDNF are likely involved. BDNF regulates neural plasticity, resilience and neurogenesis (birth of neurons), and when this process is disturbed, the hippocampus, frontal cortex, and anterior cingulate suffer. This can affect mood, along with memory and learning ability. 

Drugs that treat depression, such as Prozac, cause a change in the brain’s neurons. These drugs alter the signaling of BDNF. The drugs help form more neural connections to BDNF, thus helping treat the mood disorder.

Molecular representation of BDNF protein

Location of BDNF

Location on Chromosome

 The BDNF gene is located on chromosome 11, specifically at position 13. It has 27 base pairs, starting at base pair 27,654,892 and ending at 27,722,057 (see image above).

---

This screenshot is of the primers we chose to use in PCR to amplify BDNF. We estimated the length to be 408 base pairs long.

Charlotte's DNA and our primers were in slot 1 (the first column labeled 1 in the image to the left). In this image, you can see that our band is located around the 400 mark, which matches our estimate that it would be 408 base pairs long. You can see our estimate above.

Sources

http://upload.wikimedia.org/wikipedia/commons/8/86/Protein_BDNF_PDB_1bnd.png

http://commons.wikimedia.org/wiki/File:Protein_BDNF_PDB_1bnd.png

http://www.dnalc.org/view/2328-Changing-BDNF-Levels-with-Depression-Treatment.html

http://amedicaldiary.wordpress.com/tag/bdnf/

http://ghr.nlm.nih.gov/gene/BDNF

http://omim.org/entry/610269

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022311/

http://www.nature.com/mp/journal/v17/n6/full/mp2011107a.html

http://ghr.nlm.nih.gov/geneFamily/endogenousligands

http://www.genecards.org/cgi-bin/carddisp.pl?gene=BDNF

http://www.ncbi.nlm.nih.gov/pubmed/10486198

http://www.ncbi.nlm.nih.gov/pubmed/2133291

http://www.sinobiological.com/BDNF-Gene-a-6616.html

http://upload.wikimedia.org/wikipedia/commons/thumb/f/f0/Brain-derived_neurotrophic_factor_-_PDB_id_1BND.png/250px-Brain-derived_neurotrophic_factor_-_PDB_id_1BND.png

http://www.besthomecaremn.com/wp-content/uploads/2013/02/bigstock-Woman-Depressed-Series-2724916

http://www.eduvideo.org/wp-content/uploads/2013/11/Learning-Disability.jpg

http://braincoretherapy.com/wp-content/uploads/2014/03/anxietyattacks.jpg