Brain-derived neurotrophic factor (BDNF)

Brain-derived neurotrophic factor (BDNF) is a protein that is encoded by the BDNF gene.


It is a member of the neurotrophin family of growth factors.


Neurotrophic factors are found in the brain and the periphery. 


The BDNF protein is encoded by a gene that is also called BDNF, found  on chromosome 11.


It acts on neurons of the central nervous system and the peripheral nervous system, supporting survival of existing neurons, and encouraging growth and differentiation of new neurons and synapses.


BDNF is active in the hippocampus, cortex, and basal forebrain.

These areas are vital to learning, long-term memory, and higher thinking.


BDNF is also expressed in the retina, kidneys, prostate, motor neurons, skeletal muscle and saliva.


Parts of the adult brain retain the ability to grow new neurons from neural stem cells.


This process is known as neurogenesis. 


BDNF neurotrophins are proteins that help to stimulate and control neurogenesis.


BDNF is one of the most active neurotrophins.


Physical exercise have been shown to markedly increases BDNF synthesis in the brain, being partly responsible for exercise-induced neurogenesis and improvements in cognitive function.


Niacin upregulates BDNF and tropomyosin receptor kinase B (TrkB) expression as well.


It may modulate the activity of various neurotransmitter receptors.


The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and TrkC. 

One of the most significant effects of exercise on the brain is increased synthesis and expression of BDNF, a neuropeptide and hormone, resulting in increased signaling through its receptor tropomyosin receptor kinase B (TrkB).

Engaging in moderate-high intensity aerobic exercise such as running, swimming, and cycling increases BDNF biosynthesis through myokine signaling, resulting in up to a threefold increase in blood plasma and BDNF levels; exercise intensity is positively correlated with the magnitude of increased BDNF biosynthesis and expression.

BDNF is capable of crossing the blood–brain barrier, higher peripheral BDNF synthesis also increases BDNF signaling in the brain.

TrkB’s ligand-specific association with BDNF, expresses activity-dependent neurotic factor that regulates plasticity and is unregulated following hypoxic injury. 


The BDNF-TrkB pathway is important in the development of short-term memory and the growth of neurons.


BDNF has several known single nucleotide polymorphisms (SNP).


A common SNP in the BDNF gene is rs6265, a point mutation in the coding sequence, that interferes with normal translation and intracellular trafficking of BDNF mRNA, as it destabilizes the mRNA and renders it prone to degradation.

rs6265, the Val66Met mutation in BDNF,  results in a reduction of hippocampal tissue and is seen  in  a high number of individuals suffering from learning and memory disorders, anxiety disorders, major depression, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.


Glutamate is the glutamatergic neurotransmitter and its release can trigger the depolarization of postsynaptic neurons. 


AMPA and NMDA receptors are two ionotropic glutamate receptors involved in glutamatergic neurotransmission.


AMPA and NMDA receptors are essential to learning and memory via long-term potentiation. 


NMDA receptor activation is essential to producing the activity-dependent molecular changes involved in the formation of new memories. 


BDNF is capable of initiating synapse formation through its effects on NMDA receptor activity, but it can also support the regular every-day signaling necessary for stable memory function.


BDNF maintains elevated levels of neuronal excitation is through preventing GABAergic signaling activities.


Glutamate is the brain’s major excitatory neurotransmitter and phosphorylation normally activates receptors, GABA is the brain’s primary inhibitory neurotransmitter and phosphorylation of GABAA receptors tend to reduce their activity.


BDNF also enhances synaptogenesis. 


Synaptogenesis depends on  the assembly of new synapses and the disassembly of old synapses by β-adducin.


Adducin membrane-skeletal proteins  cap the growing ends of actin filaments and promote their association with spectrin, another cytoskeletal protein, to create stable and integrated cytoskeletal networks.


BDNF plays a significant role in neurogenesis, promoting protective pathways and inhibit damaging pathways in the neural stem cells and NPCs that contribute to the brain’s neurogenic response by enhancing cell survival. 


Studies demonstrating BDNF is a strong promoter of neuronal differentiation.


BDNF expression is significantly enhanced by environmental enrichment and appears to be the primary source of the ability of environmental enrichments to enhance cognitive processes. 


Environmental enrichment enhances synaptogenesis, dendridogenesis, and neurogenesis, leading to improved performance on various learning and memory tasks. 


BDNF is strongly regulated by calcium activity making it incredibly sensitive to neuronal activity.


Links between BDNF and depression, schizophrenia, obsessive-compulsive disorder, Alzheimer’s disease, Huntington’s disease, Rett syndrome,

dementia, as well as anorexia nervosa and bulimia nervosa.


BDNF is critical for the survival of central nervous system (CNS) and peripheral nervous system (PNS) neurons and synaptogenesis during and even after development.


BDNF abnormalities may play a role in the pathogenesis of schizophrenia. 

BDNF os located within many areas of the brain.


BDNF plays an important role in supporting the formation of memories.

BDNF mRNA levels are decreased in cortical layers of the dorsolateral prefrontal cortex of schizophrenic patients, an area involved with working memory.


Atrophy of the hippocampus and other limbic structures has been shown to take place in humans suffering from chronic depression as is associated with decreased levels of BDNF.


This suggests that an etiological link between the development of depression and BDNF exists. 


The excitatory neurotransmitter glutamate, exercise, caloric restriction, intellectual stimulation, and various treatments for depression such as antidepressants increase expression of BDNF in the brain. 


Post mortem studies has shown lowered levels of BDNF in the brain tissues of people with Alzheimer’s disease.


Epilepsy has also been linked with polymorphisms in 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.


BDNF levels are highly regulated throughout the lifetime both in the early developmental stages and in the later stages of life. 


BDNF appears to be critical for the morphological development such as dendrite orientation and number along with soma size.


Neuron morphology is critical in behavioral processes like learning and motor skills development. 


The  interaction between BDNF and TrkB, which is the receptor to BDNF, is important in inducing dendritic growth.


BDNF and active TrkB interaction appears to be necessary during a critical developmental period as it is regulatory in neuron morphology.


BDNF levels decrease in tissues with aging.


Hippocampal volume decreases with decreasing plasma levels of BDNF.

BDNF helps mediate of vulnerability to stress, memory of fear/trauma, and stress-related disorders such as post-traumatic stress disorder.


BDNF levels are high with increased itching in eczema.


It  is a regulator of drug addiction and psychological dependence. 

BDNF is a short-term promoter, but a long-term inhibitor of pain sensitivity, as a result of its effect as inducer of neuronal differentiation.


BDNF and IL-6 might be involved in post-chemotherapy chemo brain and fatigue.


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