Brain-derived neurotrophic factor
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Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found in the brain and the periphery. It is a protein that acts on certain neurons of the central nervous system and the peripheral nervous system, helping 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).
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 in 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 in the brain. It is also expressed in the retina, the CNS, motor neurons, the kidneys, and the prostate.
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[edit] 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 (source?). 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,[1] caloric restriction, intellectual stimulation, curcumin 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.[citation needed]
[edit] 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", also known as p75). It also might bind to nicotinic acetylcholine receptor alpha7.[2]
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 and NT-4,TrkA binds and is activated by NGF, and TrkC binds and is activated by NT-3. NT-3 binds to TrkA and TrkB as well, but with less affinity.
The other BDNF receptor, the p75, plays a somewhat less clear role. Some researchers have shown the p75NTR binds and serves as a "sink" for neurotrophins. Cells which express both the p75NTR 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 p75NTR may signal a cell to die via apoptosis - so therefore cells expressing the p75NTR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.
[edit] Other diseases associated with low BDNF levels
Various studies have shown possible links between low levels of BDNF and conditions such as depression, schizophrenia, Obsessive-compulsive disorder, Alzheimer's disease, Huntington's disease, Rett syndrome, and dementia, as well as anorexia nervosa and bulimia nervosa, though it is still not known whether these levels represent a cause or a symptom. [3][citation needed]
[edit] High BDNF levels
High levels of BDNF and Substance P have been found associated with increased itching in eczema.[4]
[edit] 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.[5] 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.
[edit] Genetics
The BDNF protein is coded by the gene that is also called BDNF. In humans this gene is located on chromosome 11. Val66Met (rs6265) is a single nucleotide polymorphism in the gene where adenine and guanine alleles vary resulting in a variation between valine and methionine at codon 66.
As of 2008 Val66Met is probably the most investigated SNP of the BDNF gene but besides this variant other SNPs in the gene are C270T, rs7103411, rs2030324, rs2203877, rs2049045 and rs7124442
The polymorphism Thr2Ile is may be linked to congenital central hypoventilation syndrome.[6][7]
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