- <div style="background-image:url(/live/image/gid/32/width/1600/height/300/crop/1/41839_V14Cover_Lynch_Artwork.2.rev.1520229233.png)"/>
The Life of M
Lake Forest College
Lake Forest, Illinois 60045
Hello, reader, my name is M, and I am a medium spiny neuron. My name might seem harsh, but I am quite a nice cell. I help my human body coordinate its movements along with millions of my friends in the striatum. It is because of my home that my tale is one of death and tragedy, but I am getting ahead of myself. If you wish to learn what has befallen my friends and I, read on, and hear the story of my life, the life of a neuron.
Let’s start at the beginning, as I relive the first moments of my life as a stem cell. The first thing I feel upon entering life is a sense of limitless potential and endless freedom. Energy courses through my body as I wait beneath the ventricles for life to reveal what it has in store for me. Without warning, a tingling sensation fills me. A frantic look around me identifies the source as small particles, proteins, swarming my body. Before I can open my mouth to question them, my shape has changed not once, but twice, and the proteins quickly disperse. The sense of potential I felt now begins to fade, replaced with a single focus, becoming a neuron. As I collect my newfound thoughts, I hear a gentle voice call out to me, “Come M, grab onto me and begin your journey. Your time here is over, and now your life begins.”.
“Who are you?” I respond, looking around for the source of the voice. “What happened to me?”
“You have undergone a change, one of many. You are no longer a stem cell, and now you must join your peers and fulfill your duty to the body. I am a radial glia, and I am here to help you on your journey.”
My eyes land upon the speaker, a towering, tree-trunk like cell. Before I can think, an invisible force pulls me towards it, and in an instant, I am climbing on the glia. I climb for what seems like miles, making my way outwards, waiting for the invisible force to pull me once more. My wait is not in vain, as suddenly I leave the glia’s rigid stalk, and move through an endless web of neurons, the striatum. As I find my place among my peers, I feel once more the swarming of proteins, and the changing of my body. Just as before, I am left evolved as the proteins depart, filled with a greater sense of purpose and duty. A passion fills me, as I take my shape as a medium spiny neuron. I feel a great love for movement, an action in its most literal sense, a love that will guide me until the day I die.
No longer do I feel aimless, and within moments I know what actions I must take. In my current shape, I cannot speak with my peers, as I lack the long axon and wide branching dendritic tree of a mature neuron. To fulfill my purpose in the brain, and reach my final shape; I must grow. I push with all my might on either side of my body, sending my limbs out across the brain. My axon and dendrites are surrounded by proteins who guide them and prevent unwanted connections from forming as I carelessly expand. Without the proteins, I would connect to every neuron I pass, creating chaos where there needs to be order. At last, as I tire, I slow my expansion. Although I continue to form new connections, and strengthen the bonds I have already made, the time for rapid expansion is over, and the time to commence my work has begun. Information fills my brain, as the connections I have formed begin to take shape, sending and receiving signals that cause me to jump into action. Every second I relay thousands of signals from the thousands of synapses that I have helped to form. Muscles contract and relax as my work continues, only ceasing in their responses when brief moments of calm fall over me. My life becomes one of constant action, but I feel no sadness for the lost quiet of my youth, as there is little to life without a purpose, and I have finally found mine.
Time begins to fly past me as I am caught up in the busyness of my work. For a while, I enjoy my life of maturity, but, on what seemed to be an average day, perhaps fifty years into my life, that all came to an end. “I feel something wrong with me.” A friend remarked.
“What?” I replied.
“My nucleus… I can’t seem to get anything into or out of it. It’s like it’s sealed off.”
“I’m sure it’s nothing,” I said, looking down, “but let me know if it continues.”
As there was nothing I could do for my friend, I returned to my duties, wondering why no microglia, our police, were there to protect him. Sometime later, I heard a cry, and as I turned my head to look for its source, I saw my friend dead.
“Oh my God!” I exclaimed.
“Look at his nucleus!” Cried another neuron, “It’s completely collapsed!”.
It was true, his nucleus, his brain, looked as though a rock had caved it in. As news of the death spread, an air of worry filled the brain. It was not long before my friend’s illness seemed to spread. Many thousands more deaths followed before we noticed the cause floating around us, small, misshapen, proteins.
“No one who died remembered taking in any weird-looking proteins.” I pointed out one day, wondering what caused our horrible dilemma.
“Yeah,” replied one of my neighbors, “And how would they have gotten in anyway? Barely anything makes it in here, we should be safe!”
More neurons began to join in, all eager to discuss the troubling proteins.
“If something had entered the brain, the microglia should have found it, unless it was something we made.”
“I would never make something so terrible! If we are the cause, it must be a mistake, an error in our DNA!”
A solemn quiet fell upon the brain as we realized that we were right. Only we could have made the proteins that now kill us. We do not wish harm upon our friends, nor do we wish harm upon ourselves, but a cruel twist of fate has trust upon us defective DNA, and with it a murderous protein of our own making that we can do nothing to stop.
As more neurons died, we survivors have had to pick up the slack. Millions of synapses have fallen quiet, making even our normal duties feel like a struggle. Our brain continues to survive despite our growing difficulties, but I worry that it might fail at any moment. At fifty-five years of age, my time has come. Misshapen proteins fill my body, and with a crack, I feel my nucleus collapse. I have lived a long life, and for that I am grateful, but as the world slowly fades to black, I can’t help but to feel as though my time has come too soon.
-Medium spiny neurons make up 95% of neurons in the striatum, a portion of the basal ganglia that helps to control voluntary movement. The striatum is also an area of the brain effected by Huntington’s Disease.
-The ventricles are structures in the center of the brain that are filled with cerebral spinal fluid. They serve many purposes, including helping to remove waste from the brain, and acting as a cushion when the brain receives a physical blow.
-All neurons begin life as a neuronal stem cell. These stem cells transform into neural progenitor cells, who then differentiate into either neuroblasts or glioblasts, depending on whether they will make a neuron or glia, respectively.
-Neurotrophic factors are peptides and proteins which help the cell to differentiate, causing its change from a stem cell to a neuroblast to, in this case, a medium spiny neuron. Neurotrophic factors also help nerve cells migrate.
-Radial glia act as scaffolding, or ladders, for migrating nerve cells. The nerve cells literally climb the glia until they reach the location they are programmed to be, at which point, they spread out from the glia.
-Tropic factors help to guide the growing axons and dendrites of neurons, using chemo-attractants and chemo-repulsers to promote or prevent growth/synaptic connections, respectively.
-A single neuron can form thousands of synaptic connections, allowing vast networks of neurons to send signals to each other and coordinate information.
-Microglia are the immune cells of the brain, and act to engulf debris and foreign bodies in the CNS.
-Few things are allowed to enter the brain, as the blood-brain barrier keep out all but very specific, essential, things.
-Huntington’s Disease (HD), the disease that effects the human in the story, is caused by mutant Htt proteins. A single gene mutation in the Htt gene on chromosome 4 causes abnormally long glutamine sequences to form in the mutant proteins. These proteins then damage cells in two major ways. Firstly, they disrupt nucleocytoplasmic transport but blocking transport proteins. This stops proteins from entering the nucleus, mRNA from leaving the nucleus, and also causes a greatly increased frequency of DNA double strand breaks, compared to healthy cells. Secondly, the mutant Htt causes the nuclear envelope of effected cells to weaken, and eventually collapse, leading to cell death. HD has a major impact on the basal ganglia, first effecting the striatum, which is a part of the aforementioned structure.
Before I began writing this paper, I went through some of the class materials and made notes of important events in a neuron’s life. I also looked over my journal club paper so that I could use information about HD I learned in my story. From here, I spent a great deal of time brainstorming not only what events to include, and how to work my way from one to the other, but also how to structure a story in the first person, as it has been many years since I have written a story from that point of view. After preparing for the paper as such, I spent an entire day slowly working through a first draft of my paper. In this draft, I chose to write about a neuron sharing his life story with the nearby “children” (young neurons). Though I originally thought this would be a good way to incorporate both informative body paragraphs and dialogue into a story, I didn’t like the initial result, and after writing about 2/3rds of the paper, I deleted it. I rewrote the entire paper with the same character and overarching idea, but after finishing it, I was unhappy both with the amount of information present in my story, and with the fact that I was 300 words above the maximum limit. As I find rewriting to be easier than any amount of intensive editing, I once more deleted my paper and wrote the final draft. In this draft, I decided that it would be much more consistent, and easy to follow, if I wrote about the life of a neuron as the neuron lived it. Whether it was simply luck, or if I was right in this sense, I feel as though this third and final draft of my paper includes much more information than the first two and does it in a way that flows much better and is more pleasant to read. After finishing this draft, I was once again 200 words above the limit, and thus, unfortunately had to delete portions of the story mentioning myelination, neural Darwinism, and some other miscellaneous information. After reaching the word limit, I reread the story thrice in order to make sure that it made sense, flowed in a way that I was happy with, and that all of the grammar was correct and in the right tense.
Gasset-Rosa, F., Chillon-Marinas, C., Goginashvili, A., Atwal, R. S., Artates, J. W., Tabet, R., … Lagier-Tourenne, C. Polyglutamine-expanded huntingtin exacerbates age-related disruption of nuclear integrity and nucleocytoplasmic transport. Neuron, 94, 48-57.e44. doi:10.1016/j.neuron.2017.03.027
Grubin, D. (Director). (2002). The secret life of the brain. In D. Grubin (Executive Producer), The Secret Life of the Brain: PBS.
Kolb, B., Whishaw, I. Q., & Tesky, G. C. (2016). An introduction to brain and behavior (fifth ed.). New York: Worth Publishers.
 Though not a neuron yet, M has gained a greater sense of purpose as he, with the help of neurotrophic factors, has differentiated from a stem cell, who can become whatever they wish to be, to a progenitor cell, and then a neuroblast. Neuroblasts have much more narrow focuses, as they can only differentiate into neurons.
 M, with the help of the radial glia and neurotrophic factors, migrated from the ventricular zone, where neural stem cells are, to the striatum.
 M has differentiated, with the help of neurotrophic factors, into a medium-spiny neuron, a projection neuron which resides in the striatum, and helps to coordinate motor responses.
 With the help of tropic factors, M grow out his axon and dendrites to make thousands of synaptic connections with other neurons. The tropic factors guided his axon and dendrite using chemo-attractants to promote connections, and chemo-repulsers to prevent connections.
 In Huntington’s Disease (HD), mutant Htt proteins disrupts nucleocytoplasmic transport, preventing transport proteins from functioning properly, and bringing materials into or out of the nucleus.
 Microglia are the immune cells of the brain, and act to protect nerve cells from foreign, or otherwise noticeably harmful, bodies.
 In HD, the nuclear envelope of effected cells weakens, and eventually collapses. This collapse leads to cell death.
 Though Htt proteins should not be able to leave the cells, in HD they manage to accumulate extracellularly.
 The mutant Htt found in HD is cause by a single gene mutation in the Htt gene on chromosome 4. This mutation causes abnormally long glutamine sequences to form in the mutant proteins. Cells make these mutant proteins, as they would wild-type Htt, despite the harm that will eventually come from them.
 HD is characterized by issues involving muscle movements, a consequence of mass cell death in areas of the brain related to motor control.
Eukaryon is published by students at Lake Forest College, who are solely responsible for its content. The views expressed in Eukaryon do not necessarily reflect those of the College.
Articles published within Eukaryon should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.