BDNF acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support survival of existing neurons, and encouraging 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 is also expressed in the retina, kidneys, prostate, motor neurons, and skeletal muscle, and is also found in saliva.
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BDNF Is Important For Long-Term Memory
BDNF itself is important for long-term memory.
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 proteins which 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.
BDNF And Neurotrophins Are Related
Other important neurotrophins structurally related to BDNF include NT-3, NT-4, and NGF.
BDNF is made in the endoplasmic reticulum and secreted from dense-core vesicles. It binds carboxypeptidase E (CPE), and disruption of this binding has been proposed to cause the loss of sorting 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 Can Increase BDNF Synthesis In The Human Brain
Certain types of physical exercise have been shown to markedly (threefold) increase BDNF synthesis in the human brain, a phenomenon which is partly responsible for exercise-induced neurogenesis and improvements in cognitive function.
Niacin appears to upregulate BDNF and tropomyosin receptor kinase B (TrkB) expression as well.
Links Between BNDF And Depression, Schizophrenia, OCD, Alzheimer’s and Other Diseases
Various studies have shown possible links between 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.
Increased levels of BDNF can induce a change to an opiate-dependent-like reward state when expressed in the ventral tegmental area in rats.
As of 2002 clinical trials in which BDNF was delivered into the central nervous system (CNS) of humans with various neurodegenerative disease had all failed.
Schizophrenia
See also: Epigenetics of schizophrenia § Methylation of BDNF
A plethora of recent evidence suggests the linkage between schizophrenia and BDNF.
Given that 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 alterations may play a role in the pathogenesis of schizophrenia.
BDNF has been found within many areas of the brain and plays an important role in supporting the formation of memories.
It has been shown that BDNF mRNA levels are decreased in cortical layers IV and V of the dorsolateral prefrontal cortex of schizophrenic patients, an area that is known to be involved with working memory.
Since schizophrenic patients often suffer from impairments in working memory, and BDNF mRNA levels have been shown to be decreased in the DLPFC of schizophrenic patients,
it is highly likely that BDNF plays some role in the etiology of this neurodevelopmental disorder of the CNS.
Depression
See also: Epigenetics of depression § Brain-derived neurotrophic factor
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.
Chronic Depression
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,[82] caloric restriction, intellectual stimulation, and various treatments for depression such as antidepressants[83] increase expression of BDNF in the brain.
There is evidence that antidepressant drugs protect against or reverse hippocampal atrophy.
Alzheimer's disease
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.
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 mechanism for the observed up-regulation.
Aging
BDNF levels appear to be highly regulated throughout the lifetime both in the early developmental stages and in the later stages of life. For example, BDNF appears to be critical for the morphological development such as dendrite orientation and number along with soma size.
This is important as neuron morphology is critical in behavioral processes like learning and motor skills development.
Research has reported that the interaction between BDNF and TrkB (the receptor to BDNF) is highly important in inducing dendritic growth; some have noted that the phosphorylation of TrkB by another molecule, cdk5 is necessary for this interaction to occur.
Thus, high BDNF and active TrkB interaction appears to be necessary during a critical developmental period as it is regulatory in neuron morphology.
BDNF May Decrease With Aging
Although BDNF is needed in the developmental stages, BDNF levels have been shown to decrease in tissues with aging.
Studies using human subjects have found that hippocampal volume decreases with decreasing plasma levels of BDNF.
Although this does not mean BDNF necessarily impacts hippocampal volume, it does suggest there is a relationship that might explain some of the cognitive decline that occurs during aging.
Miscellaneous
BDNF is a critical mediator of vulnerability to stress, memory of fear/trauma, and stress-related disorders such as post-traumatic stress disorder.
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).
High levels of BDNF and Substance P have been associated with increased itching in eczema.
BDNF is a regulator of drug addiction and psychological dependence. Animals chronically exposed to drugs of abuse show increased levels of BDNF in the ventral tegmental area (VTA) of the brain, and when BDNF is injected directly into the VTA of rats, the animals act as if they are addicted to and psychologically dependent upon opiates.
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.
The polymorphism Thr2Ile may be linked to congenital central hypoventilation syndrome.
BDNF and IL-6 might be involved in the pathogenesis of post-chemotherapy cognitive impairment (PCCI, also known as chemo brain) and fatigue.
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A new agent for the brain diseases: mRNA
Tokyo Medical and Dental University (TMDU) researchers prepared a nanomicelle delivery system to transport BDNF mRNA to the site of ischemic injury. The nanomicelle successfully produced BDNF and prevented the death of neurons when dosed 2 days after ischemia in rats. Long-term experiments showed significant improvements in memory compared with untreated rats. The findings are expected to extend the potential treatment window for preventing neuronal death after ischemic attack, and significantly improve outcomes for patients.
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