BDNF (Brain Derived Neurotrophic Factor) is involved in neuronal survival and growth, as well as neurotransmitter modulation and neuronal plasticity, all of which are necessary for learning and memory.

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BDNF Overview

BDNF (brain-derived neurotrophic factor) is a neurotrophic factor that promotes the differentiation, maturation, and lifespan of neurons in the nervous system. It also has a neuroprotective impact in the presence of glutamatergic stimulation, cerebral ischemia, hypoglycemia, and neurotoxicity. BDNF protein and mRNA have been found in most brain locations, including the olfactory bulb, cortex, hippocampus, basal forebrain, mesencephalon, hypothalamus, brainstem, and spinal cord, and it stimulates and controls the creation of new neurons from neural stem cells (neurogenesis). Many neurodegenerative illnesses, such as Parkinson's disease (PD), multiple sclerosis (MS), and Huntington's disease, cause BDNF levels to drop. Aside from its neuroprotective properties, BDNF is important for maintaining energy homeostasis. Peripheral or intracerebroventricular (ICV) injection of BDNF lowers energy intake and reduces body weight.

Gene Information

Mouse Gene Name: BDNF
Uniprot: P23560
Entrez: 627
Family: NGF-beta family
Alternative Names: Abrineurin; ANON2; BDNF; Brain-Derived Neurotrophic Factor; BULN2; MGC34632; Neurotrophin
Mass (kDA): 27.818 kDA

Structure of BDNF

BDNF is structurally similar to NGF and shares around half of its amino acid sequence with NGF, NT-3, and NT-4/5. Each neurotrophin is made up of a non-covalently linked homodimer that includes a signal peptide after the initiation codon and a pro-region with an N-linked glycosylation site. The BDNF gene is found on chromosome 11 in rats and is regulated by multiple activity-dependent and tissue-specific promoters I, II, III, and IV; promoters I and III are regulated by cAMP response-element binding protein (CREB) and upstream stimulatory factor-1/2 (USF-1/2), and promoter III is mediated by calcium responsive transcription factor (CaRF). Except for human exons VIIB and VIII, all exons that have been defined in humans are expressed in mouse and rat. Exon II of the rat BDNF gene is thought to undergo cryptic splicing, resulting in the IIA, IIB, and IIC genes.

BDNF Receptors

Tropomyosin receptor kinase B (TrkB) is the high affinity receptor for BDNF and NT-4/5, TrkA is for NGF, and TrkC is for NT-3. TrkB has two different isoforms. The full-length receptor glycoprotein (gp145TrkB) (M. Wt 145 kDa) and its truncated version (gp95TrkB) (M. Wt 95 kDa) without the tyrosine kinase domain, as well as the LNGFR (low affinity nerve growth factor receptor, also known as p75 NTR). Both pro- and anti-trophic activities including neurite development and apoptosis have been linked to p75 NTR. In the brain, BDNF and gp145TrkB are broadly expressed and plentiful. BDNF receptors can be found in the cells of the spinal cord as well as the grey matter of the spinal cord.

BDNF mechanism of ACTion


Through TrkB receptors, neurotrophin signaling controls cell survival, proliferation, the fate of neural progenitors, and axon and dendritic growth. The NTRK2 gene in humans codes for neurotrophic tyrosine kinase. TrkB has an extracellular domain with several glycosylation sites, a distinct transmembrane region, and an intracellular domain with Trk activity. Several small G proteins, including Ras, as well as MAP kinase, PI3-kinase, and phospholipase-C (PLC) pathways, are regulated when Ras is activated. TrkB activation takes the shortest time (2 minutes), whereas inactivation takes 30 minutes following activation in the spinal cord. The production of intermediates in various signaling pathways that affect the location of distinct signaling constituents controls Trk receptor-mediated signaling.


When BDNF binds to its high-affinity receptor, tyrosine kinase B (TrkB), it recruits proteins that activate three distinct signaling pathways. The insulin receptor substrate-1 (IRS-1/2), phosphatidylinositol-3-kinase (PI-3K), and protein kinase B are all activated in a cascade (Akt). The activation of Shc/Grb2, Ras, Raf, mitogen-activated protein kinase kinases (MEKs), and extracellular signal-regulated kinases (ERKs) is the second (ERKs). Phospholipase C (PLC), inositol (1,4,5)-triphosphate [Ins(1,4,5)P3], diacylglycerol (DAG), and protein kinase C are all involved in the third cascade (PKC). One or more transcription factors (cAMP-response-element-binding protein (CREB) and CREB-binding protein (CBP)) that regulate expression of genes encoding proteins involved in brain plasticity, stress resistance, and cell survival are activated by BDNF signaling pathways.

Activation of secondary messengers

The activation of the Trk family of receptors, TrkA-C, and the p75 neurotrophin receptor, mediates the cellular effects of neurotrophins. The massive presynaptic p75 NTR modulates Trk receptor binding, Ras-mediated activation of ERK and neurite outgrowth, as well as activating c-jun N-terminal kinase (JNK), which causes apoptosis in a variety of neurons. The MAP/ERK pathway, proto-oncogene c-fos, and nitric oxide (NO)-producing neurons are among the secondary messengers activated in the spinal cord by BDNF signaling.

BDNF Functions


BDNF's role in promoting the survival of peripheral sensory neurons during brain development was one of the first in vivo functions discovered. Exogenous administration of BDNF in the developing visual cortex resulted in increased dendritic length and complexity of pyramidal neurons in a layer-specific way, implying that BDNF not only boosted neuronal growth but also controlled a specific pattern in dendritic growth. Inhibition of spontaneous electrical activity, synaptic transmission, or L-type calcium channels also blocked exogenous BDNF-induced dendritic development, implying that neurons must be active enough to respond to BDNF's growth-promoting function.

Synaptic plasticity

Pre- and post-synaptic processes are implicated in the regulation of activity-dependent synaptic plasticity by BDNF. In cultured neocortical neurons of BDNF-knockout mice, BDNF is required for pre-synaptic vesicle cycling, which is dependent on NMDA (N-methyl D-aspartate) receptor activation. This paracrine (retrograde messenger) role of BDNF was further verified, with BDNF administration to hippocampus sections restoring spine actin polymerization and LTP (long-term potentiation) stability in rats. Furthermore, BDNF levels boosted not only NMDA levels and intracellular calcium concentrations, but also reduced Mg2+ inhibition of NMDA receptors, facilitating long-term synaptic activity modifications. LTP induction was inhibited when TrkB and BDNF production were lowered. Thus, BDNF affects NMDA receptor trafficking by increasing calcium influx, which leads to post-synaptic BDNF release, which promotes pre-synaptic vesicle cycling, enhancing LTP and synaptic plasticity.

Actions on cardiac and endothelial cells

Adult endothelial cells (EC), vascular smooth muscle cells (VSMC), and cardiomyocytes all benefit from neurotrophins, which enhance angiogenesis and regulate survival. The TrkB receptor was found to enhance therapeutic neovascularization, whereas the low-affinity receptor p75 NTR not only caused death in endothelial cells and vascular smooth muscles, but also inhibited angiogenesis. NT-3 and BDNF are important in the creation of heart and myocardial vasculature, according to research conducted in a murine BDNF knockout model. TrkB receptors on endothelial cells improve EC survival by activating two key signaling pathways, ERK/MAPK and PI3-kinase/AKT. AKT also stimulated endothelial nitric oxide (NO) synthase, which leads to vascular relaxation, which could explain its cardiovascular protection.

BDNF role in immunity

Increased levels of neurotrophins (NTs) may have a role in the development of bronchial hyperreactivity (BHR), a hallmark of allergic asthma, as evidenced by the production of NTs by immune cells such as B-lymphocytes, eosinophils, mast cells, and macrophages . CD4+ T cells are thought to create BDNF when stimulated with antigen (Ag) via shortened gp95TrkB. (expressed in non-neuronal tissues). By boosting airway smooth muscle contraction and mucus hypersecretion and accelerating the release of acetyl choline and plasma extravasation, BDNF may operate as a mediator between airway inflammatory events and neural alterations that occur during the induction of allergic asthma. In neuro-inflammatory illnesses like multiple sclerosis, however, increased production of BDNF may occur, which may have neuro-protective properties due to its immunomodulatory function. As a result, BDNF has the potential to be exploited as a therapeutic method in the identification and prevention of neurological inflammatory illnesses.

The role of BDNF in disorders of neuronal degeneration, such as multiple sclerosis. After crossing the blood-brain barrier, the antigen drives the creation of T cells, which activate B cells and macrophages. Multiple sclerosis is caused by damage to nerve fibers caused by complement fixation or antibody-dependent cell-mediated immunity. Neuroprotective processes such as BDNF release may be triggered by neuroinflammatory reactions.

Clinical significance of BDNF

From the preceding study, it is clear that BDNF has a number of critical functions that potentially have therapeutic implications. As previously mentioned, BDNF expression is reduced in a variety of neurological illnesses, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and bipolar disorder. Physical activity raises BDNF levels in the brain, which helps to alleviate sadness. Lithium, which is used to treat bipolar illness, has been shown to increase TrkB activation and BDNF mRNA expression, implying that BDNF plays a role in bipolar disorder. Overexpression of BDNF in the hippocampus has been linked to spontaneous seizures, which can develop to temporal lobe epilepsy. Furthermore, rabbit intestinal smooth muscle cells (SMCs) produce and release BDNF, which is controlled by calcium release, which activates substance-P (SP) and pituitary adenylate cyclase activating peptide (PACAP).

By activating the PLC pathway, BDNF can modify gut function and hence has therapeutic potential in the treatment of irritable bowel syndrome and functional dyspepsia.

In autism, there was a significant drop in the levels of BDNF-BCl2-Akt (genes implicated in BDNF's anti-apoptotic signaling pathways). As a result, BDNF levels in the blood could be utilized as a biomarker to detect autism in its early stages. As previously stated, BDNF plays a critical function in energy homeostasis, which explains its role in obesity, type 2 diabetes, and metabolic syndrome. BDNF appears to be capable of preventing type 2 diabetes mellitus through both peripheral and central effects.