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Eukaryon

Life of a Neuron: The Parkinson’s Apocalypse in Paul Kepler

Jaleesa Lalani
Lake Forest College
Lake Forest, Illinois 60045

I wasn’t there to see the beginning, but the eldest neurons often described it to me. They would re-enact the story of how we came to be where we are. When I was younger, we were all gathered in the neural tube. It began with just two cells; they were young and, like me, unassigned. Those two spilt to form two more, and those split, and this continued until the first tissue was formed. A groove formed in this tissue, and it eventually folded into a closed tube that began to grow as the cells continued to multiply.[1] That was a long time ago, but all the new stem cells still begin in the same neural tube, before they move to their place and get their assignments. The elders also told us stories of the importance of working together and doing our jobs as best as we can. They told us of a lovely little human baby named Paul Kepler. They said we all were a small but important part of making his life good and happy.

 

Moving to my permanent spot was a scary process, and it is usually difficult for most of us. Migration is the first time that we are entirely independent, and because of that a lot of cells don’t make it. We were shown the map at first and introduced to the radial glial cell that we would be following. From there, I was on my own to follow the rope and find my spot in the substantia nigra.[2]

 

When I arrived, others also began to settle around me and we read out the instructions that we had. They came from a large roll wound like a helix, and it told everyone what their job was and where they were supposed to stay. I was assigned to be a dopaminergic neuron, responsible for synapsing dopamine that would eventually help Paul Kepler to contract his muscles and move. My job was very important, and I needed to meet many other cells to be successful. To become a neuron took a few tries, and I got it wrong at first but eventually I fully differentiated. [3]

 

Once I had my job and my place, I thought that I was fully settled and that it would be easy going forward. How wrong I was. For my whole life I have needed to be socializing, synapsing and making connections with other cells, and it was especially intense and important during maturation. At this time, my dendrites had begun growing in, and I was all-too aware of my ever-expanding surface area. To compensate, I began a wild search for good targets, and I worked hard to extend my axons and create synapses.[4] Although it was tough, it certainly paid off.

 

We had just celebrated our 63rd year of work when I first heard of the news. Bits and fragments passed from cell to cell like whispers. From what I pieced together, a large cluster of cells had begun dying randomly, and no one knew why. We accepted the news with unease, although life continued much the same as we worked away normally. Slowly, we heard more and more often about these random deaths until they began happening to some of my synapsed cells. I noticed one day that I hadn’t gotten messages from some of my closer connections in quite a while. I reached out, but they didn’t respond. Turning to my oldest and strongest connection, I shared my fears with my best friend Bill. Although he agreed with me, he had no idea what could be happening, and so we had no choice but to wait and see what would become of us.

 

It wasn’t long after this that strange events began happening right around us. Bill told me about the scared-looking alpha-synuclein that asked him for shelter one day. No one really knew what alpha-synuclein did, but it introduced himself as Lewy and asked politely, so he seemed harmless, and Bill let him in.[5] Bill was a good guy, but he’d made a big mistake. Days went by and I watched as Lewy cajoled Bill into “just one small favor” or “one quick thing” until he was so busy and tired that he could hardly get his work done. His responses became weak and  passed on less and less dopamine.[6] I was sick with worry, but Bill insisted he was fine and let Lewy stay. Lewy had grown immensely and was steadily taking over Bill’s life. He wasn’t able to work anymore, and he started to shut down. Terrified for him, I tried to help Bill in any way I could think of, but I was too late. Bill shut down completely, and there wasn’t anything I could have done to save him.  

 

Immediately after Bill’s death, I connected the dots and concluded the lying, scheming Lewy body was to blame. Not long after, another close connection told me of a story about a Lewy similar to Bill’s. Furious, I tried my best to compensate for the loss of Bill and other neurons. I worked overtime, tiring myself out constantly attempting to send signals, but it seemed as if they weren’t getting anywhere. I think Paul Kepler was also trying to help externally. Much more dopamine than usual was showing up, and I tried my best to pass it on.[7] When that didn’t work, the enzymes that usually cleared excess dopamine began to shut down and the amount that I had available boosted somewhat.[8] I just couldn’t seem to send enough of it out to change anything. I found out later that because of all the cells that had already been lost, no amount of work that I did would have made a difference.

 

Devastated, I fought to keep working, but I became tired and weak from the stress. I lost the defense to fight off the Lewy that came for me, and now he has taken root. I suppose soon I will meet the same fate as my dear friend Bill. I am sorry, Paul Kepler, I know I lived to help you throughout your life, but there is nothing else that I can do now. I hope that you will continue to fight this, although I am not sure there is a way to win. Regardless, remember the 71 years of life that our work created for you and appreciate them for what they were. I hope that I did my job well and that I served the purpose that my DNA instructed me to.

 

List of Neurobiological Concepts:

  • Neural tube development
  • Migration
  • Differentiation
  • Maturation and synaptogenesis
  • Introduction of alpha-synuclein
  • Development of Lewy bodies
  • Cell death in the Substantia nigra because of Lewy bodies
  • Use of dopamine-boosting drugs as a treatment option
  • Use of MOA inhibitors as a treatment option

 

Writing Process:

Beginning to write this paper was very similar to how I approached papers 1 and 2. I began by reading the rubric and prompt and annotating and highlighting. I looked for clues about structure, content and overarching themes. Using this, I created a blank outline of my idea for the paper based on the prompt. For this paper, I started researching using the textbook and notes from class, then I expanded to notes from the PBS series, and finally I turned to the internet. Most of my online sources are Parkinson’s specific, as they are more up to date and in-depth than the textbook. Once I had completed my research, I filled out the blank outline and added in storyline ideas where I had them. From here, I used the outline to create the paper. For this assignment, I tried to write as freely as possible. This made for a longer editing process to cut down, but I feel like it allowed me to get deeper into my ideas so that they came across as more developed in the final version. Overall, considering that I am not much of a fan of creative writing, I like the paper I wrote. I think I was able to incorporate enough scientific information that it has a factual background while still holding somewhat true to a storyline.

 

Bibliography:

ATrain Education. (n.d.). Retrieved from https://www.atrainceu.com/course-module-short-view/2441043-143_parkinsons-module-02

Brain Basics: The Life and Death of a Neuron. (2018, November 06). Retrieved from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Life-and-Death-Neuron

Burciu, G, R., Ofori, Edward, Archer, B, D., … E, D. (2017, July 26). Progression marker of Parkinson’s disease: A 4-year multi-site imaging study. Retrieved from https://academic.oup.com/brain/article/140/8/2183/4032257

David Grubin Productions in association with Thirteen/WNET New York. (2002). The secret life of the brain. [Alexandria, Va.] :PBS Home Video,

Fearnley, J. M., & Lees, A. J. (1991, October). Ageing and Parkinson’s disease: Substantia nigra regional selectivity. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1933245

How Does Parkinson’s Disease Develop? (n.d.). Retrieved from https://parkinsonsdisease.net/basics/pathophysiology-what-is-it/

Kolb, B., & Whishaw, I. Q. (n.d.). Understanding and Treating Neurological Disorders. In An Introduction to Brain and Behaviour (4th ed., pp. 589-592). Lethbridge, AB: Worth Publisher.

Mandybur, G., & Gartner, M. (2018, April). Parkinson’s Disease (PD). Retrieved from https://www.mayfieldclinic.com/PE-PD.htm

Micheal, P. P., Hirsch, E. C., & Hunot, S. (2016, May 18). Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. Retrieved from https://www.sciencedirect.com/science/article/pii/S0896627316300587

Stages of Parkinson’s. (2018, October 17). Retrieved from https://parkinson.org/Understanding-Parkinsons/What-is-Parkinsons/Stages-of-Parkinsons

Timmer, J. (2010, November 12). Why neurons die in Parkinson’s patients. Retrieved from https://arstechnica.com/science/2010/11/why-neurons-die-in-parkinsons-patients/

 

[1] Neural tube development

[2] Migration

[3] Differentiation

[4] Maturation and Synaptogenesis

[5] Introduction of Alpha-synuclein

[6] Development of Lewy bodies

[7] Use of dopamine-boosting drugs as treatment option

[8] Use of MOA inhibitors as treatment option

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