Research Mentor Name

Dr. Thummel

Research Mentor Email Address

rthummel@med.wayne.edu

Institution / Department

Wayne State University School of Medicine, Department of Ophthalmology, Visual and Anatomical Sciences

Document Type

Research Abstract

Research Type

basicbio

Level of Research

no

Abstract

Purpose: Genetic leukoencephalopathies (gLEs) are heritable white matter disorders of the nervous system that produce severe motor impairment, cortical blindness, intellectual disability, and seizures. Recent evidence shows that a mutation in Vacuolar Protein Sorting 11 (VPS11) causes an autosomal recessive gLE in humans and that vps11(plt) mutant zebrafish can model the disease. Clemastine, an FDA approved drug, benefits patients with multiple sclerosis and enhances oligodendrocyte differentiation and number in zebrafish. In this study, we aim to determine whether Clemastine treatment will improve visuomotor function in our vps11(plt) mutant zebrafish.

Methods: Wild type (WT) and vps11(plt) mutant (MUT) lines were separated into 3 groups and treated for 2 days with embryo medium (EM), 0.1% DMSO, or 500nM of Clemastine (CLM). At 7 days post fertilization, the Noldus DanioVision system tracked zebrafish movement in response to alternating light and dark cycles.

Results: WT and MUT zebrafish travelled significantly more distance and velocity in the dark than in light. MUTs moved significantly less distance and velocity overall compared to WT. We found no significant difference between EM WT and CLM WT groups nor between EM MUT and CLM MUT groups in distance traveled or velocity.

Conclusion: These data showed that Clemastine had no impact on the behavior of vps11 (plt) mutant zebrafish. Future studies will determine if Clemastine increases oligodendrocyte number in our zebrafish mutant model, as was previously shown in WT zebrafish. If so, this would indicate that increased oligodendrocyte number does not necessarily equate to functional outcomes of improved motor responses.

Disciplines

Medicine and Health Sciences

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