Investigating cerebellar Pathology in a zebrafish C9orf72 ALS model
Amyotrophic Lateral Sclerosis (ALS) is a rare and fatal disease, which is characterized by degeneration of specific neurons called “Motor neurons” that control the movement of our muscles. We are particularly interested in a specific gene called C9ORF72, which is found to be mutated in most of the ALS cases. The cerebellum is a brain region that controls balance and movement coordination but its role has been widely overlooked in ALS studies, despite emerging evidences of cerebellar degeneration in ALS. We hypothesize that the C9ORF72 gene might have something to do with the cerebellum function and movement dysfunction observed in ALS.
Main goals in this project:
Understanding the Brain Changes: We developed an animal (zebrafish) model to study C9orf72 ALS. We now want to figure out how the brain of zebrafish (a type of fish used in research because they have similar genes to humans) with a c9orf72 gene problem are different from normal fish. We will look at the fish’s brain cells structure and function within the cerebellum.
Early Warning Signs: We are also looking to see if changes in the cerebellum happen before or along with motor neuron degeneration, which could give us clues about how ALS starts and/or progresses.
Connecting Brain Changes to Movement Problems: We are interested in seeing if the brain changes caused by c9orf72 gene dysfunction are connected to problems with movement. We will track the fish movements and see if there’s a link between their brain changes and how they swim.
Finding Out Why Brain Cells Die: Finally, we are curious to understand why the cells within the cerebellum die in fish with the c9orf72 gene dysfunction. We will look at the specific genes in these cells using an innovative technique -called Single Cell transcriptomic- to see what might be causing them to die.
This research is important because it could help us understand ALS better and potentially find new ways to treat it. By looking closely at the cerebellum and how it’s connected to ALS at a cellular and molecular level, we hope to uncover important clues that could lead to better treatments for this disease.
Jaskaran Singh , Institut national de la recherche scientifique (INRS)
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