Ant Murphy

ENGW3307
Musselman
1/25/2015 Unit 1 Final Draft
CSE Citation
Word Count: 1199
Glutamates Role in Neurodegenerative Disease and Why You Should Care, Too
I find neuroscience particularly fascinating because you get to study the working mechanisms
behind our ability to sense the world around us and interact with it. I have been lucky enough to work in a
couple labs focusing on the nervous system during my undergraduate program here at Northeastern, both
on and off campus, piquing my interest in neurobiology. My freshman year I was able to do a directed
study under my biological inquiries professor studying the brain and in particular circadian rhythms. I
learned a lot about structure of the brain and how to stain and look at brain tissue, skills I used to get a coop in a lab where I worked on a couple different projects dealing with the Central Nervous System, or
CNS The CNS is the part of the nervous system which is, contained within the brain and spinal cord, as
opposed to the PNS, or Peripheral Nervous System, or the nerve cells in the rest of the body that collect
information to send back to the brain. I decided to use a literary review by Ankita et al 2013 focusing on a
specific neurotransmitter in the CNS, how it contributes to common neurodegenerative diseases, and
where we may focus next to further our understanding.
The neuron is the basic unit of the nervous system; it is typically a long cell (some types of
neurons in the spine can be incredibly long a single cell can reach an entire meter in length) (Debanne et
al 2011) which convey electrical signals from one end of the cell to the other. There are many different
types of neurons, but every kind has to be able to communicate with other neurons in order to function
properly. This is done through the use of neurotransmitters, chemicals which are released by a presynaptic
neuron and travel through the space between neurons called the synapse to be received by the
postsynaptic neuron, which propagates the signal on to the next cell and so on. Neurotransmitters are
crucial for the functioning of the nervous system, and arguably the most important one is called
glutamate; glutamate is the most abundant neurotransmitter in the CNS and is crucial for communication
between neurons in the spinal cord and brain (Ankita et al 2013).
Although glutamate is essential to the functioning of the brain, it can actually be damaging in
high amounts. An excess of glutamate can cause a phenomenon called excitotoxicity, when neurons
become too excited by a large influx of chemical signals and open their pores to let in excessive
amounts of other substances {Ankita et al 2013}. It is important to note that this toxicity has nothing to do
with the chemical properties of glutamate. Despite how some people feel about MSG (also known as
monosodium glutamate), glutamate itself is not harmful to typical human cells; as an amino acid it

belongs to the same class of chemicals that make up all human proteins for use in a countless number of
functions {Ankita et al 2013}. However, cells which have glutamate receptors (neurons and glial cells)
are susceptible to the excitotoxicity effect that excess glutamate can cause. There are different kinds of
receptors and transporters that allow cells to interact with glutamate, such as a transporter called xCT.
xCT is a transporter I studied during a co-op that helps to transport glutamate out of cells, increasing the
concentration of extracellular glutamate, thereby increasing the risk of excitotoxicity. Therefore, neurons
are not only susceptible to damage from glutamate excitotoxicity, but can also contribute to the problem.
This problem is more common than it may sound as it is often an effect of neurodegenerative
diseases, such as Parkinsons, Alzheimers, Huntingtons or Multiple Sclerosis {Ankita et al 2013}.
Diseases like these effect many people worldwide,
Alzheimers alone is present in over 5 million Americans and
is the 6th leading cause of death in the US (Alzheimers
Association 2015), so there is a great interest in dampening
the effects of glutamate excitotoxicity to help reduce
inflammation and loss of neuronal function in patients
(Ankita et al 2013). This was exactly our goal when working
with xCT; we thought that if we could block this glutamate
transporter in Multiple Sclerosis (MS) patients extracellular
glutamate would decrease resulting in dampened
excitotoxicity. Although this would not cure MS, it could

Figure 1: SMI-32 staining in a

diseased mouse spinal cord. Damaged
neurons shown as a dark brown
speckling

potentially treat some serious symptoms such as

inflammation in the brain and overall decreased brain
function.
Currently there are many methods being tested to help patients with glutamate problems,
including the use of stem cells, gene therapy, and monoclonal antibodies to develop not only treatments
for symptoms but potentially preventative medicine as well (Ankita et al 2013). At Genzyme, we used
monoclonal and polyclonal antibodies to aid us in learning more about xCT and the disease state of MS.
Figure 1, a photo I took of tissue I stained during my co-op, shows how antibodies can be used to
visualize damage in neurons in MS models. I used an antibody called SMI-32 that binds to damaged
axons before staining it brown so we could quantify the amount of damage done to the axons caused by
glutamate excitotoxicity. The use of antibodies can be more complex when using multiple types of
antibodies and fluorescent labels. Figure 2, another photo of my work at Genzyme, shows the use of two
types of fluorescently tagged antibodies that attach to the xCT receptor and to glial cells called microglia

in red and teal, respectively. Glial cells are

helper cells in the brain which aid axons in
various ways by maintaining extracellular
concentrations of chemicals and acting as the
immune system of the brain, among other
things. Circled is a cell which shows staining
with both antibodies, indicating that some
microglia do in fact contain this transporter.
Even with these techniques, discovering new
drugs is expensive and time consuming
Figure 2: Dual fluorescent labeling of xCT and Iba1
(for tagging microglia) in teal and red, respectively.
Dark blue staining is nuclear staining to visualize
individual cells.

(Ankita et al 2013). More research needs to

be done on these molecular pathways so that
we can better understand what drives these
neurodegenerative disease states (Ankita et

al 2013). I hope to get the chance to make larger contributions in the future and now that I have a couple
labs down on my resume it might actually be possible. I am starting another co-op in the summer, so it
looks like I wont have to hold my breath for very long.

Literature Cited

Mehta Ankita, Prabhakar Mayank, Kumar Puneet, Deshmukh Rahul, Sharma PI, Excitotoxicity: Bridge
to various triggers in neurodegenerative disorders, European Journal of Pharmacology, January 2013.
Debanne Dominique, Campanac Emilie, Bialowas Andrzej, Carlier Edmond, Alcaraz Gisele, Axon
Physiology, Physiological Reviews vol. 91, 1 April 2011
Alzheimers Association website, Facts and Figures,
http://www.alz.org/alzheimers_disease_facts_and_figures.asp, visited 1 January 2015

Acknowledgements
Maria Albrecht, for proof reading my 1st draft when she probably had better things to do.