Brain-derived neurotrophic factor
Encyclopedia
Brain-derived neurotrophic factor, also known as BDNF, is a protein
that, 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.
s 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 synapse
s.
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 mammal
ian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cell
s 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
.
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 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 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 that the p75NTR binds and serves as a "sink" for neurotrophins. Cells that 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.
and secreted from dense-core vesicles. It binds carboxypeptidase E
(CPE), and the disruption of this binding has been proposed to cause the 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 humans.
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
allele
s 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 may be linked to congenital central hypoventilation syndrome
.
In 2009, variants close to the BDNF gene were found to be associated with obesity
in two very large genome wide-association studies of body mass index
(BMI).
, schizophrenia
, obsessive-compulsive disorder
, Alzheimer's disease
, Huntington's disease
, Rett syndrome
, and dementia
, as well as anorexia nervosa
and bulimia nervosa
.
Increased levels of BDNF can induce a change to an opiate-dependent-like
reward state when expressed in the ventral tegmental area in rats.
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 between the development of depression and BDNF exists. Supporting this, the excitatory neurotransmitter glutamate, voluntary exercise, caloric restriction, intellectual stimulation, curcumin
and various treatments for depression (such as antidepressant
s and electroconvulsive therapy
and sleep deprivation) 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.
have been found associated with increased itching in eczema
.
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 mechanism for the observed up-regulation.
, although the nature of the connection remains unclear. Studies suggest that neurotrophic factors have a protective role against amyloid beta
toxicity.
with TrkB
. BDNF has also been shown to interact with the reelin
signaling chain. The expression of reelin by Cajal-Retzius cell
s goes down during development under the influence of BDNF. The latter also decreases reelin expression in neuronal culture.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that, in humans, is encoded by the BDNF gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. BDNF is a member of the "neurotrophin
Neurotrophin
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...
" family of growth factors, which are related to the canonical "Nerve Growth Factor", NGF
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
. Neurotrophic factors are found in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
and the periphery.
Function
BDNF acts on certain neuronNeuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
s.
In the brain, it is active in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
, cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, and basal forebrain
Basal forebrain
The basal forebrain is a collection of structures located ventrally to the striatum. It is considered to be the major cholinergic output of the central nervous system . It includes a group of structures that lie near the bottom of the front of the brain, including the nucleus basalis, diagonal band...
—areas vital to learning, memory, and higher thinking.
BDNF itself is important for long-term memory
Long-term memory
Long-term memory is memory in which associations among items are stored, as part of the theory of a dual-store memory model. According to the theory, long term memory differs structurally and functionally from working memory or short-term memory, which ostensibly stores items for only around 20–30...
.
BDNF was the second neurotrophic factor to be characterized after nerve growth factor (NGF
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
).
Although the vast majority of neurons in the mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s in a process known as neurogenesis
Neurogenesis
Neurogenesis is the process by which neurons are generated from neural stem and progenitor cells. Most active during pre-natal development, neurogenesis is responsible for populating the growing brain with neurons. Recently neurogenesis was shown to continue in several small parts of the brain of...
. 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
Neural development
Neural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...
.
Tissue distribution
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 the prostate. BDNF is present in high concentration in hippocampus and cerebral cortex. BDNF is also found in human saliva.Mechanism of action
BDNF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkBTrkB
TrkB receptor also known as TrkB tyrosine kinase or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene.-Function:...
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 receptor
Alpha-7 nicotinic receptor
The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor, consisting entirely of α7 subunits....
.
TrkB
TrkB
TrkB receptor also known as TrkB tyrosine kinase or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene.-Function:...
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
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
and TrkC
TrkC
NT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene....
. Also, there are other neurotrophic factors structurally related to BDNF: NGF
NGF
NGF may refer to:*Nerve growth factor*Naval gunfire*Northern Group of Forces*National Golf Foundation*North German Federation...
(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
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
binds and is activated by NGF, and TrkC
TrkC
NT-3 growth factor receptor also known as neurotrophic tyrosine kinase receptor type 3 or TrkC tyrosine kinase or Trk-C receptor is a protein that in humans is encoded by the NTRK3 gene....
binds and is activated by NT-3. NT-3 binds to TrkA
TrkA
High affinity nerve growth factor receptor also known as neurotrophic tyrosine kinase receptor type 1 or TRK1-transforming tyrosine kinase protein or Trk-A is a protein that in humans is encoded by the NTRK1 gene....
and TrkB as well, but with less affinity.
The other BDNF receptor, the p75, plays a somewhat less clear role. Some researchers have shown that the p75NTR binds and serves as a "sink" for neurotrophins. Cells that 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.
Secretion
BDNF is made in the endoplasmic reticulumEndoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
and secreted from dense-core vesicles. It binds carboxypeptidase E
Carboxypeptidase E
Carboxypeptidase E, also known as carboxypeptidase H and enkephalin convertase, is an enzyme that in humans is encoded by the CPE gene....
(CPE), and the disruption of this binding has been proposed to cause the loss of sorting of BDNF into dense-core vesicles. The phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
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
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
levels in the rodent hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
, suggesting the potential increase of this neurotrophin after exercise in humans.
Genetics
The BDNF protein is coded by the geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that is also called BDNF.
In humans this gene is located on chromosome 11.
Val66Met (rs6265) is a single nucleotide polymorphism
Single nucleotide polymorphism
A single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...
in the gene where adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
and guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
s vary, resulting in a variation between valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
and methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
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 may be linked to congenital central hypoventilation syndrome
Ondine's curse
Ondine's Curse, also called congenital central hypoventilation syndrome or primary alveolar hypoventilation, is a respiratory disorder that is fatal if untreated...
.
In 2009, variants close to the BDNF gene were found to be associated with obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
in two very large genome wide-association studies of body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
(BMI).
Disease linkage
Various studies have shown possible links between BDNF and conditions, such as depressionClinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
, Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
, Rett syndrome
Rett syndrome
Rett syndrome is a neurodevelopmental disorder of the grey matter of the brain that almost exclusively affects females. The clinical features include small hands and feet and a deceleration of the rate of head growth . Repetitive hand movements, such as wringing and/or repeatedly putting hands into...
, and dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, as well as anorexia nervosa
Anorexia nervosa
Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...
and bulimia nervosa
Bulimia nervosa
Bulimia nervosa is an eating disorder characterized by binge eating and purging or consuming a large amount of food in a short amount of time, followed by an attempt to rid oneself of the food consumed, usually by purging and/or by laxative, diuretics or excessive exercise. Bulimia nervosa is...
.
Increased levels of BDNF can induce a change to an opiate-dependent-like
Opiate dependency
Opioid dependency is a medical diagnosis characterized by an individual's inability to stop using opioids even when objectively it is in his or her best interest to do so...
reward state when expressed in the ventral tegmental area in rats.
Depression
Exposure to stressStress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
and the stress hormone corticosterone
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...
has been shown to decrease the expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of BDNF in rats, and, if exposure is persistent, this leads to an eventual atrophy of the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
. Atrophy of the hippocampus and other limbic structures has been shown to take place in humans suffering from chronic depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
. 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 between the development of depression and BDNF exists. Supporting this, the excitatory neurotransmitter glutamate, voluntary exercise, caloric restriction, intellectual stimulation, curcumin
Curcumin
Curcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family . The other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are natural phenols and are responsible for the yellow color of turmeric...
and various treatments for depression (such as antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
s and electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...
and sleep deprivation) 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.
Eczema
High levels of BDNF and Substance PSubstance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
have been found associated with increased itching in eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
.
Epilepsy
EpilepsyEpilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
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 mechanism for the observed up-regulation.
Alzheimer's disease
Post mortem analysis has shown lowered levels of BDNF in the brain tissues of people with Alzheimer's diseaseAlzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, although the nature of the connection remains unclear. Studies suggest that neurotrophic factors have a protective role against amyloid beta
Amyloid beta
Amyloid beta is a peptide of 36–43 amino acids that is processed from the Amyloid precursor protein. While it is most commonly known in association with Alzheimer's disease, it does not exist specifically to cause disease...
toxicity.
Interactions
Brain-derived neurotrophic factor has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with TrkB
TrkB
TrkB receptor also known as TrkB tyrosine kinase or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene.-Function:...
. BDNF has also been shown to interact with the reelin
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
signaling chain. The expression of reelin by Cajal-Retzius cell
Cajal-Retzius cell
The term Cajal–Retzius cell is applied to reelin-producing neurons of the human embryonic marginal zone which display, as a salient feature, radial ascending processes that contact the pial surface, and a horizontal axon plexus located in the deep marginal zone...
s goes down during development under the influence of BDNF. The latter also decreases reelin expression in neuronal culture.