Research Question
My research question for this summer is:
“Are synaptic defects the first defects in neurodegenerative diseases?”
Before I started, the PIK3C3 gene was removed from mutant mice to model neurodegenerative diseases. The PIK3C3 gene is involved in membrane trafficking (exocytosis and endocytosis) and is necessary to maintain a functional neuron, so removing it from the mutant mice has understandably caused some neurological problems. We’ve already seen older mutant mice (9 months old) develop neurodegenerative diseases, with notable differences in morphology between the mutant and control mice of the same age. As the mice age, neurons begin to die in the mutants, and we would like to figure out why this happens.
The first step was to determine at what age the brains of mutant mice began showing morphological differences from the brains of control mice. I’m doing this through retrograde detection, so I’ll start with older mice and keep analyzing younger mice until I find the age at which there aren’t morphological differences between the control and mutant mice. I started with 3 month old mice. I sectioned the brains of two different mice, one control and one mutant. Then I stained them to analyze the abundance and organization of neurons and glial cells. Some symptoms that affect the mutant mice are neuron apoptosis and gliosis, so in a mutant mouse we would expect to see a greater number of glial cells and fewer or deformed neurons, when compared to the control mouse. This is what I observed in the 3-month-old mice, which means that even though they aren’t showing outward symptoms of neurological degeneration, their brains have already been affected.
Now, I’m going to take a look at the brains of mice that are about 1 month old to detect morphological differences. With mice this young, we don’t expect to see overwhelming differences between the control and mutant mice, so this is the age during which I will be looking for synaptic differences. We’re hoping that the only difference between mutant and control mice are synaptic defects in the mutants.
So why is this important? I’m going to use Alzheimer’s Disease as an example, because it’s common, but this applies to neurodegenerative diseases in general. When someone develops Alzheimer’s Disease, they show symptoms gradually. But even before the smallest symptoms are shown, their brain has been affected. By the time the symptoms are great enough to warrant a trip to the doctor and a diagnosis, it’s already way too late. The only thing doctors can hope to do is slow the progressions of the disease because it’s very, very difficult to reverse neurodegenerative diseases. If we can figure out what happens first during neurodegenerative diseases (again, we think synaptic defects come first), then we can begin the process of figuring out how to reverse/prevent/treat/etc. the disease.
