This is a guest blog by Kelly Siemund from the University of Leipzig in Germany.
I am an early-career researcher in neuroscience, specifically working on one of the most common forms of MND: Amyotrophic Lateral Sclerosis (ALS). I obtained my master’s degree in biology with a major in neuroscience. My interest in neuroscience was initially sparked after volunteering for a year and a half at a center for mentally disabled individuals. My experience there created a desire to contribute to advancing our knowledge in neurodegenerative disease research and finding solutions for brain disorders. During my undergraduate studies at the University of Leipzig, Germany, I received a scholarship from the Erasmus Program to participate in a research project abroad for my master’s thesis. For this purpose, I joined an amazing research group in Budapest, Hungary, working on animal models of epilepsy. After working in this area for a year and completing my master’s degree, I was admitted to a PhD research project at the Carl Ludwig Institute of Physiology of the medical faculty of the University of Leipzig in Germany, where I have been working on MND under the supervision of Dr. Christian Simon. This is how I was first introduced to MND research.
What does your work focus on?
Throughout my PhD, I have investigated changes in the connections between neurons, called synapses, in a mouse model of ALS. This project, financed by the German Research Foundation, aims to understand more about the links between the loss of brain cell signals and the death of motor neurons in ALS. ALS is characterized by the dysfunction and degeneration of upper and lower motor neurons, leading to muscle weakness and muscle atrophy. Many factors contribute to motor neuron loss, including the loss of incoming signals from other cells to motor neurons. Synapse signals onto motor neurons can either be excitatory or inhibitory, that is, they can either activate motor neurons or prevent their activity. Synapses form the communication highway between upper and lower motor neurons and muscles. An imbalance in motor neuron activity, revealed by too much or insufficient activity, contributes to motor neuron damage and death. Therefore, synaptic inputs onto motor neurons are essential for their function and survival and thus vital for muscle strength. My work focuses on establishing the link between the loss of synapses and the death of motor neurons in the spinal cord.
Why is this research important?
While it is clear that synapses, as well as motor neurons, are damaged and die as ALS progresses, it is still not known how or why this happens throughout the disease. My work aims to answer questions like “What synapses are specifically affected in these diseases as motor neurons die?”, “In what regions of the spinal cord are these synapses mostly affected?” and “How does the loss of synapses link with motor neuron death in ALS?”. To answer these questions, I used detailed microscopes to investigate spinal motor neuron death and synapse loss in mouse models of ALS.
Considering the importance of synapse signals in the spinal cord and their impact on motor function, my work will contribute to shedding light on the spinal cord regions where signaling is most affected and to what extent it is impaired. My research will also advance our knowledge of the progression of ALS in mice.
What have you found so far?
Just as specific muscle groups might be more vulnerable to damage in ALS, some spinal cord regions are more affected than others. Previous studies show that certain motor neuron groups die at early symptomatic stages of the disease while others are more affected at the final stages of the disease. Accordingly, synaptic connections in the spinal cord are lost at various stages of the disease and to different extents. My work so far shows that although sensory synapses are consistently altered in distinct spinal cord regions, their onset and the severity of their impairment depend on the area of the spinal cord investigated. Understanding this region-specific loss of synaptic function with the death of spinal motor neurons is essential to comprehending disease progression and targeting biomarkers involved in disease pathways.
What are the next steps for this research?
Working with an animal model of ALS broadened my knowledge and understanding of MND and neurodegenerative diseases. I am eager to pursue my postdoctoral research work on ALS research to further explore this disease and hopefully make a greater contribution to this field. Considering the crucial role that synaptic connections play in motor function and how much they are affected in ALS, I am interested in investigating further their impact on motor neuron death in vulnerable spinal cord regions. This could help to determine whether altering the functions of these synapses could slow down and eventually prevent motor neuron loss. Furthermore, I am excited to target specific biomarkers that trigger synaptic loss and motor neuron death in ALS. Discovering the key players in these events may help to understand the exact mechanism of motor neuron death and disease progression in ALS.
My research contributes to the outstanding work done around the globe to unravel the underlying mechanisms of MND and eventually discover new biomarkers that will lead to new treatments. My current research and future projects will enhance our understanding of the biology of ALS and aid in discovering new biological markers that can be used in successful clinical trials for people affected by ALS.
We would like to thank Kelly for giving her time to write this blog about her work.
