Neuronal Traffic Jams Explained Using Isogeometric Analysis-Based Models

Neurons, tiny cells which make up the human brain, consist of a cell body and one or several processes projecting from this cell body. In most neurons with many projections, one of these processes, the axon, is prominent and may extend over a variable distance from the cell body before dividing into several terminals. While it is in fact true that synthesis of most products occurs in the cell body, there is a flow between it and the axon which allows materials to travel to the axon terminals from the cell body and vice versa. These axonal flows are referred to as anterograde and retrograde transport respectively and require certain scaffold cytoplasmic proteins known as microtubules. This transport, though just one out of the many marvels of the neuron, is largely important as it forms the key means by which nutrients get to the axon terminals from the cell body and send certain materials back to the cell body. As such, in conditions like Alzheimer’s, Huntington’s, and Parkinson’s disease where this mechanism is impaired following an overload of this process, degeneration of the axon distal to the site of overload is a very common feature. Modeling this intricate process has been the goal of scientists Jessica Zhang and Angran Li from Carnegie Mellon University and in one of their recent studies published in Scientific Reports, they successfully modeled this material transport regulation.

Read Also: Scientists’ Newest Discovery Gives Greater Insight into the World of Neuronal Communication

Neuronal Activity

Neuronal Activity

Understanding the cause of neuronal traffic jams

To understand the mechanism behind the neuronal traffic jams observed in the brain, the team used isogeometric analysis (IGA) to accurately model the neurons studied. Their study focused on “traffic jams” seen in these pathways, and the neurons modeled were obtained from a database of digitally-reconstructed models of real neurons, neuromorpho.org.

Their results showed that a reduction in the number of functional microtubules in the area affects the volume of materials the axon can transport leading to congestion of materials in the axon. They also found that the distance materials had to cover increased with axonal swelling or microtubule swirling. However, as the materials spread out, they occupy space and risk causing imbalances that further affect their transport, and with time, as observed in microtubule depletions, “neuron traffic jams” occur.

Clinical significance

Neurodegeneration following congestion of materials in axons is a common phenomenon seen in the pathogenesis of diseases like Parkinson’s. While this study does not offer therapy to counteract this occurrence, it provides clarity regarding how it occurs which could help fine-tune the current views about this process and the diseases it’s seen in. Drugs aimed at increasing the transcription of microtubule proteins or stabilizing them may prove to be quite effective in preventing this mechanism and thus curing neurodegenerative diseases.

Read Also: Johns Hopkins’s Breathtaking Device Can Visualize Neuronal Connections in the Brain In Vivo

Conclusion

Before now, Zhang’s team has applied IGA in several programs aimed at modeling other parts of the body including the veins, and the heart with success. Like these previous programs, modeling the neuron traffic jams will not only help understand the pathogenesis of certain diseases but will also serve as a bedrock for future research. The question now is this: what would the next research unravel?

References

Modeling material transport regulation and traffic jam in neurons using PDE-constrained optimization

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