BDNF: The Brain's Shining Star
In the vast cosmos of our brain, a star shines brightly, influencing the intricate network of neurons that shape our thoughts, memories, and emotions. This star is the Brain-Derived Neurotrophic Factor (BDNF), a vital neurotrophic factor that has captivated the attention of neuroscientists worldwide. BDNF is a vital neurotrophic factor in the brain, maintaining neuronal survival, inducing differentiation, promoting maturation, and regulating synaptic functions Deinhardt, K. and Chao, M. V., 2014)[2].
The Maestro: BDNF and Its Gene Structure
Nestled within the intricate labyrinth of human chromosome 11, the BDNF gene holds court, a complex entity composed of 11 exons and nine functioning promoters. This intricate dance of genetic material, through a process known as alternative splicing, gives birth to a variety of unique BDNF transcripts, each a different blueprint, yet all leading to the creation of the same pre-pro-protein. The metamorphosis of pro-BDNF into its mature form, mBDNF, can occur within the cell's confines or outside the extracellular space.
Figure 1: Genomic structure of both the human BDNF and rodent Bdnf genes. Exons are colored according to between-study and between-species analogy. Exons are shown as boxes, whereas introns are shown as lines. Figure redrawn and adapted from Pruunsild and others (2007).
This choice echoes with profound implications for the brain's circuitry and the malleability of synaptic connections. The gene's narrative doesn't end there; it harbors two distinct polyadenylated transcription stop sites, giving rise to mRNA molecules with either short or long 3' untranslated regions (UTRs). These subtle variations in the mRNA's architecture are pivotal in shaping the neuronal landscape. Interestingly, the presence of BDNF transcripts is not confined to the cerebral realm alone; they have been discovered in peripheral blood cells, hinting at their potential as signposts for psychiatric conditions. Notably, BDNF transcripts IV and IX levels surge in peripheral blood cells and the hippocampus, indicating their significant role in the grand symphony of BDNF expression. [Cattaneo, A., Cattane, N., et al., 2016 [5], Notaras, M., van den Buuse, M., 2018 [6]
Interestingly, proBDNF and mature BDNF (mBDNF) have unique roles in the grand theater of the brain. Like the two sides of a coin, these isoforms interact with different receptors and initiate distinct signaling pathways that determine the fate of neurons. The balance between these two forms is a delicate dance, varying depending on the stages and regions of brain development, underscoring the intricate nature of BDNF's function (Colucci-D'amato, L., Speranza, L., Volpicelli, F., 2020) [1]. Moreover, discoveries of BDNF isoforms, such as a shorted BDNF protein known as truncated BDNF protein, whose complete biology still needs to be thoroughly examined. [https://pubmed.ncbi.nlm.nih.gov/23825634/][7] demonstrates the incredible diversity of BDNF and provides plentiful opportunities for future research.
The Score: BDNF's Signaling, Expression and Release
BDNF, much like a maestro conducting an orchestra, orchestrates a symphony of functions within our brain. It is encoded by a complex gene structure with multiple exons and alternative promoters, each playing a unique part in the grand composition of our neural processes (Colucci-D'amato, L., Speranza, L., Volpicelli, F., 2020) [1].In the great tapestry of the nervous system, the Brain-derived neurotrophic factor (BDNF) assumes a pivotal role, orchestrating the modulation of synaptic activity. The symphony of signals between BDNF and its receptor, tropomyosin receptor kinase B (TrkB), is implicated in a multitude of cellular processes, from the transcription and translation of genetic information to the trafficking of proteins during synaptic development.
The BDNF-TrkB signaling pathway, according to an expanding body of evidence, also wields considerable influence over synaptic plasticity. This term refers to the dynamic capacity of synapses to either strengthen or weaken over time, a process intimately intertwined with learning and memory formation mechanisms.
A trio of distinct pathways facilitates the execution of these cognitive tasks: the mitogen-activated protein kinase (MAPK), phospholipase CG (PLC/PLCG), and phosphatidylinositol 3-kinase (PI3K). The proteins PI3K and MAPK serve as crucial mediators in the processes of protein translation and transport triggered by synaptic activation. Meanwhile, the protein PLCG regulates intracellular calcium (Ca2+) levels, subsequently stimulating gene transcription via the cyclic AMP pathway.
The cosmos of the nervous system is delicately balanced, and compelling evidence suggests that deviations from normal levels of BDNF can profoundly impact the onset and progression of various developmental and neurodegenerative disorders. This is primarily due to the disruptive effects of abnormal BDNF levels on neuronal development and functioning.
A profound understanding of the regulatory role of the BDNF-TrkB pathway in synaptic activity and plasticity is of paramount importance. Such knowledge is key to developing effective therapeutic interventions for genetic dysfunctions within this system, which are associated with severe neurodevelopmental disorders.
The Performance: BDNF's Physiological Functions
In the central nervous system (CNS), BDNF plays a role as multifaceted as a prism-refracting light. It is involved in neurogenesis in the hippocampus, a brain region that is a hotbed of memory and learning (Park, H. and Poo, M. M., 2013) [3]. It also plays a part in synaptic transmission and long-term potentiation in various brain regions, processes that are fundamental to how our brain cells communicate and strengthen their connections (Park, H. and Poo, M. M., 2013 [3].
Genetic and environmental factors regulate BDNF variant expression. Many levels regulate BDNF gene expression. Blunt arrows show BDNF expression reduction, while sharp ones show the opposite. The agreement is that aging, Alzheimer's disease, and chronic stress lower BDNF levels, while several research found the contrary (dash lines). However, exercise, enriched environments, and antidepressants can boost BDNF expression. Thus, the above strategies may address cognitive deficits caused by reduced BDNF expression. Since these external factors can interact (shown by the orange circle arrow), it is necessary to consider all of these potential interactions when identifying causal linkages between these variables and BDNF expression.
The Finale: BDNF's Role in Disease
Moreover, BDNF plays a significant role in neuroprotection and brain regeneration, akin to a guardian angel watching over our brain cells. It modulates signaling pathways, ensuring our neurons recover and regenerate [1]. In the context of glioblastoma, a type of brain cancer, BDNF takes on the role of a master architect, reorganizing the microenvironment of the brain. It has the potential to resist neurodegeneration or create an oncolytic environment for tumors, demonstrating its versatility and importance [1]
The Encore: The Importance of Validated BDNF Measurement Tools
Given the importance of BDNF in the grand scheme of brain health, its accurate measurement is as crucial as the precise calculations needed to launch a spacecraft. Proper, validated BDNF measurement tools, such as the Rapid ELISA assays available at Biosensis, are critical.
These tools ensure the accurate quantification of BDNF, enabling researchers to draw reliable conclusions from their studies, much like astronomers interpreting the signals from distant stars. Learn More.
In conclusion, BDNF plays a pivotal role in the swirling cosmos of our brains, influencing various aspects of brain health. Its accurate measurement is essential for advancing our understanding of the mysteries of the brain. As research on BDNF continues to evolve, it is hoped that this knowledge will develop novel therapeutic strategies for neurodegenerative and neuropsychiatric disorders, much like how our understanding of the cosmos has led to advancements in space exploration. In the grand theater of the brain, BDNF is indeed a star that shines brightly, guiding us on our journey to unravel the mysteries of the mind.
Numbered references
- Ambigapathy, G., Zheng, Z., et al., 2013 [7] https://pubmed.ncbi.nlm.nih.gov/23825634/
- Cattaneo, A., Cattane, N., et al., 2016 [5] https://pubmed.ncbi.nlm.nih.gov/27874848/
- Colucci-D'amato, L., Speranza, L., Volpicelli, F., 2020) [1]. https://pubmed.ncbi.nlm.nih.gov/33096634/
- Deinhardt, K. and Chao, M. V., 2014)[2] https://pubmed.ncbi.nlm.nih.gov/23664813/
- Notaras, M., van den Buuse, M., 2018 [6] https://pubmed.ncbi.nlm.nih.gov/30387693/
- Park, H. and Poo, M. M., 2013) [3] https://pubmed.ncbi.nlm.nih.gov/23254191/
Explore and Learn More about Biosensis’ BDNF Complete portfolio