From Wikipedia, the free encyclopedia
Brain-derived neurotrophic factor also known as
BDNF is a protein
which in humans is encoded by the BDNF gene.
BDNF is a member of the "neurotrophin" family of growth factors –
which are related to the canonical "Nerve Growth Factor", NGF. Neurotrophic
factors are found in the brain and the periphery.
BDNF 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 itself is important for long-term memory.
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 central nervous system, motor neurons, the kidneys, and
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 may also modulate the activity of various neurotransmitter
receptors, including the Alpha-7 nicotinic
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
BDNF is made in the endoplasmic reticulum and secreted from
dense core vesicles. It binds the sorting receptor carboxypeptidase
E (CPE) and the disruption of this binding causes loss of sorting
of BDNF into dense core vesicles. The phenotype for BDNF knockout mice can be
severe, including postnatal lethality. Other traits include sensory
neuron losses that affect coordination, balance, hearing, taste,
and breathing. Knockout mice also exhibit cerebellar abnormalities
and an increase in the number of sympathetic neurons.
Exercise has been shown to increase the
secretion of BDNF at the mRNA and protein levels in the rodent hippocampus, suggesting
the potential increase of this neurotrophin after exercise in
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
The polymorphism Thr2Ile may be linked to congenital central
In 2009 variants close to the BDNF gene were found to
associatate with obesity in
two very large genome wide association studies of body mass index
Various studies have shown possible links between BDNF and
conditions such as depression, schizophrenia,
as well as anorexia nervosa
Increased levels of BDNF can induce a change to an opiate-dependent-like reward state when
expressed in the ventral tegmental area in
Exposure to stress and the
stress hormone corticosterone has been shown to
decrease the expression of BDNF in rats, and if
exposure is persistent this leads to an eventual atrophy of the
hippocampus. Atrophy of the hippocampus and other limbic structures
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. This suggests that an etiological link exists
between the development of depression and BDNF. Supporting this,
the excitatory neurotransmitter glutamate, voluntary exercise, caloric restriction, intellectual
stimulation, curcumin and
various treatments for depression (such as antidepressants and
electroconvulsive therapy and
increase expression of BDNF in the brain. In the case of some
treatments such as drugs
and electroconvulsive therapy this
has been shown to protect or reverse this atrophy.
High levels of BDNF and Substance P have been found associated with
increased itching in eczema.
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
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 mechanism for the observed
Post mortem analysis has shown lowered levels of BDNF in the
brain tissues of people with Alzheimer's disease, although the
nature of the connection remains unclear. Studies suggest that
neurotrophic factors have a protective role against amyloid beta toxicity.
Brain-derived neurotrophic factor has been shown to interact with TrkB.
BDNF has also been shown to interact with the reelin signaling chain.
The expression of reelin by Cajal-Retzius
cells goes down during development under the influence of
The latter also decreases reelin expression in neuronal
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