Brain-derived neurotrophic factor (BDNF) is a neuroprotective and neurogenetic factor that is one of the most common and well-known neurotrophic factors in the mammalian brain. BDNF boosts dopaminergic neuron survival, dopaminergic neurotransmission and motor function. Brain-derived neurotrophic factor BDNF has a home, though. Here is more background on the neuroprotective and neurogenic properties of BDNF in dopaminergic neurons, neurotransmitters and motor activity. BDNF is also a neuroprotective chemical - that is, something that keeps brain neurons in check. It is necessary for normal nervous system. The brain uses BDNF in neurogenesis (the generation of new neurons). BDNF increases neurogenesis and nervous system development.
BDNF could also be a learning agent for functional and structural plasticity in the CNS, in dendritic spines and (in the hippocampus at least) adult neurogenesis. Adult neural rates and spine density change – and with them learning, memory and mood. BDNF's immune modulatory role guards against neurodegeneration (think Alzheimer's, depression, neurodegenerative diseases).
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Brain-derived Neurotrophic Factor Involved in Nervous System
This Brain-derived neurotrophic factor (BDNF) protein was discovered in 1982, and it is a very conserved protein of 247 amino acids. The tropomyosin receptor kinase B (TrkB) and the low-affinity p75 neurotrophin receptor (p75NTR) transmit BDNF. BDNF is required for normal growth, development and plasticity of glutamatergic and GABAergic synapses and serotonergic and dopaminergic neurotransmission by modulating neuronal differentiation. BDNF is a paracrine and autocrine regulator both at pre- and postsynaptic targets. It is required to convert synaptic firing into persistent synaptic memory. This multifarious action by BDNF can be explained by the specificity of its multistep production through multiple intermediate bioactive isoforms that attach to different receptors and activate different signalling pathways.
Physiological Activity of Brain-derived Neurotrophic Factor
Which specific function of brain-derived neurotrophic factor (BDNF) in managing so many of these physiological activities in the brain depends on how isoforms of BDNF interact with different receptors. It then evokes the signaling circuits necessary for brain development, synaptic plasticity, and injury protection and/or repair. Failure of BDNF synthesis causes the breakdown of its signalling cascades and can trigger a number of pathologies. BDNF protein is produced in the cell bodies of neurons and glial cells across the brain, but it is abundant in the hippocampus and cortex. BDNF transcripts are transliterated into pro-BDNF in cell bodies of neurons, and cut to pro-BDNF in human neurons. If cleaved in a cell, BDNF could be packed into clumps of core vesicles and shipped to the axons and dendritic centers. Once transported, BDNF can be constitutively released, perhaps in a Ca 2+-dependent way. Its best release mechanism is patterned electrical stimulation activity-induced release.
Fig. 1 Presynaptic and postsynaptic effects of BDNF-TrkB activity (Wang, C., et al. 2022).
BDNF Transcripts
The brain-derived neurotrophic factor (BDNF) gene codes for a neurotrophic factor that is extremely abundant in the CNS. Mutations in methylation of BDNF promoter IV cause depression. MDD patients have hypomethylation of the BDNF gene promoter IV region, CpG-87, and therefore can't take antidepressants. Furthermore, deletion of BDNF promoter IV-related transcripts reduces fear in mice, indicating that BDNF from promoter IV-encoded cells modulates hippocampal-prefrontal plasticity during fear memory.
miRNA and BDNF
MicroRNAs (miRNAs) are evolutionary conserved small noncoding, single-stranded RNA molecules (18–25 nucleotides long) that bind to the 3′ untranslated region (3′UTR) of target mRNAs to degrade or prevent their translation into proteins. miRNAs are tissue-specific and widely distributed in the nervous system, and are involved in many different biological processes such as neurogenesis, neuronal development, synapse formation, axon regulation, neurite proliferation, and neuroplasticity. The synthesis of BDNF could be controlled by miRNAs and in fact, there is actually a negative regulatory feedback loop between BDNF and miRNAs. That is, although BDNF treatment promotes neuronal miRNA expression, miRNAs are normally negative for BDNF.
Role of Brain-derived Neurotrophic Factor in Neurological Disorders
The neurotrophic factor is an old field of neurodegenerative disorders. Disrupted regulation of particular neurotrophic factors and their receptors seems linked to neurodegeneration. Neurotrophic factors slow cell death and aid in growth and development of neurons, so that in AD and PD, injured neurons thrive. The aim of modern AD and PD treatments is to avoid neurodegeneration, and neurotrophic factors are now the primary cure for early, middle and even late-stage AD and PD.
Neurotrophic factors by activating the IP3K/Akt kinase network stifle cell death. We have observed low blood and brain BDNF levels in depression or PD and AD. Decreased BDNF levels in the blood and brain in PD patients correspond with the progression of more dopaminergic neuronal loss, leading to movement disorders, cognitive disorders and psychiatric symptoms, and also AD memory deficits.
BDNF neuroprotective effect results from TrkB/MAPK/ERK1/2/IP3K/Akt activation that resists oxidative stress-mediated apoptosis, glutamate and NO neurotoxicity and cell damage. Oxidative stress, glutamate neurotoxicity, NO and apoptosis spike in the brain.
Conclusion
Brain-derived neurotrophic factor (BDNF) is well known to act neuroprotectively and neurorepairingly on dopaminergic neurons, which lends itself well as a potential PD drug. Yet neither exogenous BDNF was ever delivered directly into patients' brains nor have efforts to stimulate BDNF expression with gene therapy. Properly selected exercise can impermanently boost BDNF in the blood and brain and even (in animal experiments) in some cases defend neurons from neurotoxic damage. Knowledge of how training enhances BDNF production and how BDNF causes neuroprotection and neurorepair can be used to develop drug therapies for PD and create new PD therapies.
References
- Wang, C., et al. BDNF signaling in context: From synaptic regulation to psychiatric disorders. Cell. 2022, 185(1): 62-76.
- Colucci-D'Amato, L., et al. Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. International journal of molecular sciences. 2020, 21(20): 7777.
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