Summer Research Updates and Directions: Axon Degeneration, Calcium, and Glial Cells

Hi Everyone! It has been an extremely busy summer and in this post I am going to cover what I have been doing from May up until now.

I have been culturing neurons for drug treatment to characterize the effects on axon degeneration after injury. First, I induce injury to the axons by severing them with a blade, and without any drug treatment the farther portion of the axon form the cut site degenerates over a course of about 12 hours. The implication of this degeneration in a living system is that with injury communication between neurons is impaired. After inducing axonal injury, I administer a drug with the goal of delaying the degeneration time course.  The drug that I selected is nifedipine, which is a calcium channel blocker. The logic of using this drug is due to the fact that in the axonal degeneration pathway there is a calcium influx through such calcium channels that causes the activation of certain proteases to chew up the structural components of the axon causing the physical degeneration observed. So, what if we tried blocking a number of these channels to stop the proteases from taking apart the axon? Using various dilutions of nifedipine, I found the optimal concentration to delay axon degeneration by about 12 hours. This is a significant delay, however, the fact that degeneration proceeds indicates other pathway mechanisms that ultimately allow for the activation of proteases.

The next part of my project I have been working on is building a mathematical model of this part of the axonal degeneration pathway that includes calcium homeostasis. Using Matlab, I am writing differential equations to represent the different reaction rates and interactions of the pathway to obtain the ultimate output of a degeneration time course. In this model I can introduce drug treatment, such as nifedipine, at different time points after simulating injury. The ultimate goal of the model is to mirror what I have observed in my in vitro experiments on neuronal cultures to indicate a reliable starting point to my model. The aim going into September is to build on this pathway with upstream components to build a larger, more cohesive model.

An interesting dynamic I am beginning to consider is not only the axonal degeneration pathway itself, but also the environment the injured neurons exist in, which includes other cells that release signals including microglia, oligodendrocytes, and astrocytes. I am thinking there might be some overlap between the signaling of an injured neuron with such glial cells that may facilitate the propagation of axon degeneration.  I have been performing immunohistochemistry assays on brain tissue from young specimens, old specimens, and stroke specimens to label for the prevalence of these cell types to see if there are differences among the tissue types and observe colocalization of cellular debris with these glial cells. This idea is still very new and exciting to me as I am considering ways to incorporate this dimension into my modeling.


  1. Jessica Crowley says:

    Glad to hear!

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