Arianna Antigua

Rising Junior at Brown University studying Biology and Public Health. Examined Srrm2 Heterozygous KO effects on myelin-related proteins, in different brain regions of mice of varying ages, to better understand Srrm2’s association with Schizophrenia

Large-scale exome sequencing studies have associated Srrm2 with schizophrenia. How mutations in Srrm2 lead to schizophrenia is unknown. I am going to leave you all with two quotes that allowed me to persevere through the challenges I met this summer. “Let every situation be what it is instead of what you think it should be, and then make the best of it” -Mandy Hale and “The definition of insanity is doing the same thing over and over and expecting different results” -Albert Einstein. Allow yourself to grow on this journey, and lean on your cohort and mentors for support. This is an amazing opportunity to learn more about yourself as a scientist, but you have to learn to put your ego aside and know that you are not going to have the answers to everything. The goal is not perfection, it’s progress, and with an open mind you can achieve that. Myelin sheaths–structures that insulate neuronal axons–play an important role in electrical transmission between nerves. In Srrm2 heterozygous knockout (Srrm2 +/-) mice, the expression of myelin-related genes is decreased, and the number of oligodendrocytes—cells responsible for making and maintaining myelin sheaths—is reduced in multiple brain regions. Additionally, several myelin-related proteins are reduced in sub-cellular proteomics of the cortex. These lines of evidence suggest disrupted myelination in schizophrenia, evidence of which has also been observed in humans with the disease. It is therefore of interest to examine levels of myelin-related proteins across brain regions and longitudinally over different ages in Srrm2 +/- mice. Two regions of particular interest are the hippocampus and striatum, dysfunction of which has been implicated in schizophrenia. We therefore compared the levels of key myelin proteins CNPase and MBP in the hippocampus and striatum between Srrm2 +/- and littermate controls using western blotting. We observe decreased expression of CNPase and MBP in both brain regions, with a more robust reduction in the striatum. The understanding of myelin protein reduction in Srrm2 +/- mice provides insights into the molecular mechanisms of schizophrenia and informs more targeted and effective therapeutics.

Project: Examining changes in myelin-related proteins in Srrm2 +/- mice, a genetic model of Schizophrenia

Mentors: Sameer Aryal and Chuhan Geng, Stanley Center Therapeutics