Brain-derived neurotrophic factor
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Brain-derived neurotrophic factor (BDNF), or abrineurin,
BDNF activates the
Function
BDNF acts on certain
BDNF itself is important for long-term memory.[17] Although the vast majority of neurons in the
BDNF is made in the
Mechanism of action
BDNF binds at least two receptors on the surface of cells that are capable of responding to this growth factor,
TrkB
The TrkB receptor is encoded by the
LNGFR
The role of the other BDNF receptor,
Expression
The BDNF protein is encoded by a gene that is also called BDNF, found in humans on chromosome 11.
Common SNPs in BDNF gene
BDNF has several known
Val66Met
A common SNP in the BDNF gene is rs6265.[41] This point mutation in the coding sequence, a guanine to adenine switch at position 196, results in an amino acid switch: valine to methionine exchange at codon 66, Val66Met, which is in the prodomain of BDNF.[41][40] Val66Met is unique to humans.[41][40]
The mutation interferes with normal translation and intracellular trafficking of BDNF mRNA, as it destabilizes the mRNA and renders it prone to degradation.[41] The proteins resulting from mRNA that does get translated, are not trafficked and secreted normally, as the amino acid change occurs on the portion of the prodomain where sortilin binds; and sortilin is essential for normal trafficking.[41][40][42]
The Val66Met mutation results in a reduction of hippocampal tissue and has since been reported in a high number of individuals with learning and memory disorders,[40] anxiety disorders,[43] major depression,[44] and neurodegenerative diseases such as Alzheimer's and Parkinson's.[45]
A meta-analysis indicates that the BDNF Val66Met variant is not associated with serum BDNF.[46]
Role in synaptic transmission
Glutamatergic signaling
NMDA receptor activity
NMDA receptor activation is essential to producing the activity-dependent molecular changes involved in the formation of new memories. Following exposure to an enriched environment, BDNF and NR1 phosphorylation levels are upregulated simultaneously, probably because BDNF is capable of phosphorylating NR1 subunits, in addition to its many other effects.
Synapse stability
In addition to mediating transient effects on NMDAR activation to promote memory-related molecular changes, BDNF should also initiate more stable effects that could be maintained in its absence and not depend on its expression for long term synaptic support.[54] It was previously mentioned that
GABAergic signaling
One mechanism through which BDNF appears to maintain elevated levels of neuronal excitation is through preventing
Synaptogenesis
BDNF also enhances synaptogenesis. Synaptogenesis is dependent upon the assembly of new synapses and the disassembly of old synapses by β-adducin.[59] Adducins are membrane-skeletal proteins that cap the growing ends of actin filaments and promote their association with spectrin, another cytoskeletal protein, to create stable and integrated cytoskeletal networks.[60] Actins have a variety of roles in synaptic functioning. In pre-synaptic neurons, actins are involved in synaptic vesicle recruitment and vesicle recovery following neurotransmitter release.[61] In post-synaptic neurons they can influence dendritic spine formation and retraction as well as AMPA receptor insertion and removal.[61] At their C-terminus, adducins possess a myristoylated alanine-rich C kinase substrate (MARCKS) domain which regulates their capping activity.[60] BDNF can reduce capping activities by upregulating PKC, which can bind to the adducing MRCKS domain, inhibit capping activity, and promote synaptogenesis through dendritic spine growth and disassembly and other activities.[59][61]
Dendritogenesis
Local interaction of BDNF with the TrkB receptor on a single dendritic segment is able to stimulate an increase in PSD-95 trafficking to other separate dendrites as well as to the synapses of locally stimulated neurons.
Neurogenesis
Laboratory studies indicate that BDNF may play a role in
Research
Preliminary research has focused on the possible links between BDNF and clinical conditions, such as
Schizophrenia
Preliminary studies have assessed a possible relationship between schizophrenia and BDNF.[69] 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 associated with working memory.[70]
Depression
The neurotrophic hypothesis of depression states that depression is associated with a decrease in the levels of BDNF.[66]
Epilepsy
Levels of both BDNF mRNA and BDNF protein are known to be up-regulated in epilepsy.[71]
See also
- Epigenetics of depression § Brain-derived neurotrophic factor
- Epigenetics of schizophrenia § Methylation of BDNF
- Tropomyosin receptor kinase B § Agonists
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000176697 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048482 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Anti-Brain Derived Neurotrophic Factor Antibody, pro". sigmaaldrich.com. Retrieved 20 August 2023.
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