DEK Loss Impairs Learning and Memory Without Altering Neuronal Cell Density

Abstract

By Lydia Gall, Neuropsychology; Allie Greene, University of Cincinnati; Matia Solomon, University of Cincinnati; Valentina Ghisays, University of Cincinnati

Advisor: Matia Solomon

Abstract: Alzheimer's disease is a neurodegenerative disorder that induces memory loss and confusion as well as the loss of other debilitating cognitive functions. This disease is characterized by the prevalence of tau tangles and amyloid-beta plaques that prevent neurons from making connections, leading to cell death. A proto-oncogene, DEK, has been recently thought to play a role in the brain, particularly with learning and memory. This nuclear phosphoprotein influences the cell cycle and regulates many cellular processes including DNA repair, senescence, apoptosis, and proliferation, and is postulated to be neuroprotective. Preliminary data from our lab indicates that DEK knockout mice have spatial memory deficits, further suggesting the importance of DEK for cognition. My goal was to identify the molecular mechanisms of DEK loss in the brain, primarily in the hippocampus, a region important for learning and memory. Using immunohistochemistry, I looked at neural cell type markers (GFAP, for astrocytes, and NeuN, for neurons) in DEK knockout and wild-type mice (n=3 per group). My findings suggest that there is no difference in the density and morphology of neurons and astrocytes. If DEK knockout does not impact neuron and astrocyte cell number and morphology, there could be an underlying mechanism by which DEK loss negatively impacts learning and memory. Future experiments will study the expression of learning and memory-relevant proteins, such as brain-derived neurotrophic factor (BDNF), to determine how DEK loss could influence dementia-like phenotypes.