Brain-derived neurotrophic factor

Brain-derived neurotrophic factor (BDNF) is exactly as it states; a neurotrophic factor found originally in the brain, but also found in the periphery. More specifically, it is a protein which has activity on certain neurons of the central nervous system and the peripheral nervous system; it helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses. In the brain, it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF was the second neurotrophic factor to be characterized, after nerve growth factor (NGF) and neurotrophin three (NT-3).

Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis, BDNF being one of the most active. Mice born without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system, and usually die soon after birth, suggesting that BDNF plays an important role in normal neural development.

Despite its name, BDNF is actually found in a range of tissue and cell types, not just the brain. Expression can be seen in the retina, the CNS, motor neurons, the kidneys, the prostate and more.

Effects of stress and BDNF's link in depression

Exposure to stress and the stress hormone corticosterone has been shown to decrease the expression of BDNF in rats, and leads to an eventual atrophy of the hippocampus if exposure is persistent. Similar atrophy has been shown to take place in humans suffering from chronic depression. In addition, rats bred to be heterozygous for BDNF, therefore reducing its expression, have been observed to exhibit similar hippocampal atrophy, suggesting that an etiological link between the development of depressive illness and regulation of BDNF exists. On the other hand, the excitatory neurotransmitter glutamate ^*, voluntary exercise, caloric restriction, intellectual stimulation, and various treatments for depression (such as antidepressants and electroconvulsive therapy) strongly increase expression of BDNF in the brain, and have been shown to protect against this atrophy.

Mechanism of action for BDNF

BDNF binds at least two receptors on the surface of cells which are capable of responding to this growth factor, TrkB (pronounced "Track B") and the LNGFR (for "low affinity nerve growth factor receptor).

TrkB is a receptor tyrosine kinase (meaning it mediates its actions by causing the addition of phosphate molecules on certain tyrosines in the cell, activating cellular signaling). There are other related Trk receptors, TrkA and TrkC. Also, there are other neurotrophic factors structurally related to BDNF: NGF (for Nerve Growth Factor), NT-3 (for Neurotrophin-3) and NT-4 (for Neurotrophin-4). While TrkB mediates the effects of BDNF, NT-4, and NT-3, TrkA binds and is activated by NGF, and TrkC binds and is activated by NT-3.

The other BDNF receptor, the LNGFR, plays a somewhat less clear role. Some researchers have shown the LNGFR binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity - since they have a higher "microconcentration" of the neurotrophin. It has also been shown, however, that the LNGFR may signal a cell to die via apoptosis - so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather then live in the presence of a neurotrophin.

Other diseases associated with low BDNF levels

Various studies have shown possible links between low levels of BDNF and conditions such as depression, Obsessive-compulsive disorder, Alzheimer's disease, Huntington's disease, Rett syndrome, and dementia, though it is still not known whether these levels represent a cause or a symptom.

Epilepsy

Epilepsy has also been linked with polymorphisms in BDNF. Given BDNF's vital role in the development of the landscape of the brain, there is quite a lot of room for influence on the development of neuropathologies from BDNF.

Levels of both BDNF mRNA and BDNF protein are known to be up-regulated in epilepsy. BDNF modulates excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor mediated post-synaptic currents. This provides a potential reason for the observed up-regulation.

External links

Citations

//www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8137432&query_hl=18&itool=pubmed_docsum Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development.

//www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16701206&query_hl=18&itool=pubmed_DocSum Cell Survival through Trk Neurotrophin Receptors Is Differentially Regulated by Ubiquitination

Neurotrophins