Effects of a BDNF varient on the outgrowth of hiPSC-derived motoneurons

What question are you seeking to answer?

Brain derived neurotrophic factor (BDNF) is a protein that is very important for the regeneration and growth of motor neurons. We were seeking to answer whether a specific protein variant that is common in the US population (BDNF Val66Met) influenced that rate at which motor neurons grew.

Why did you choose this topic? 

I have always had an interest in regenerative medicine, and this gave me the opportunity to build on my existing basic science research skills on a topic that could potentially change the way we approach treatment of peripheral nerve injury!

How did you study this question? 

We used stem cells that were generated from patients expressing a specific variant of the Brain Derived Neurotrophic Factor (BDNF) protein (Val66Met), and genetically edited them to make three cell lines with different genotypes. We then turned these stem cells into motor neurons for our experiments and were able to compare the results across the three groups. Using special antibodies and stains, we were able to visualize the neurons on a microscope and count which neurons grew the longest neurites, which are projections from the neuronal cell body.

What did you learn through your research?

We learned that motor neurons expressing this common variant of BDNF (Val66Met) had significantly longer neurites than the control motor neurons. This suggests that patients who possess this variant of BDNF may have enhanced growth of peripheral neurons at baseline as compared to those patients possessing the more common BDNF genotype (Val/Val).

Who stands to benefit from this research? 

Current treatments of peripheral nerve injuries (PNI) are limited, and typically involve surgical reattachment of the nerves if possible. Outside of this, various other therapies such as exercise are being tested because existing data shows that these therapies may improve outcomes following injury. Interestingly, there is evidence in mouse and rat models of peripheral nerve injury showing that exercise therapy does not improve, and in some cases impairs, peripheral nerve regeneration in mice possessing this BDNF Val66Met variant. This variant is present in 25-33% of the US population. Given the difference in outcomes seen in animal models and prevalence of this variant in the US population, this research poses the question of whether we should genotype patients who sustain a PNI and alter their rehabilitation plan based on the results. Those who sustain a PNI and possess this common BDNF variant may stand to benefit substantially from such a personalized approach.

What are the next steps in your research? 

My research focused primarily on using uninjured motoneurons to study their baseline neuronal outgrowth. The next step would be to culture these neurons and injure them, then measure potential differences in neuronal growth following this injury with and without various PNI treatments.

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