Discipline: Neuroscience
Subcategory: Cell and Molecular Biology
Session: 4
Room: Embassy
Sharee McGriff - Delaware State University
Co-Author(s): Dr. Michael A. Gitcho, Delaware Center for Neuroscience Research, Delaware State University, Dover, DE
TDP-43 is the major pathological protein in motor neuron disease (MND) (~95%) and frontotemporal dementia (FTD) (-50%). Recently, TDP-43 pathology was found in ~50% of those with Alzheimer’s disease (AD). TDP-43 pathology in astrocytes is common in the developmental disorder, Alexander’s disease but at a lower frequency in MND, FTD, AD, and other TDP-43 proteinopathies. Pathological TDP-43 becomes hyperphosphorylated, proteolytically cleaved, and shows a decrease in solubility. We hypothesize that astrocyte-specific expression of TDP-43 will induce non-cell autonomous neurodegeneration leading to memory deficits and increased anxiety-like behaviors. Our study seeks to understand astrocyte function in the context of TDP-43 pathology. We have developed and characterized a new mouse model that selectively drives human TDP-43 containing three familial ALS mutations specifically in astrocytes. Utilizing the tetracycline inducible system (GFAP-tTA), we examined 12-month-old mice for anxiety-like behavior (open field) and memory (y-maze). Immunohistology and protein analysis was also evaluated in the spinal cord and brain of these aged mice, We show significant changes in memory and anxiety-like behavior with no motor deficits. These findings will hopefully broaden our understanding into astrocyte dysfunction seen in neurodegenerative diseases and to potentially find a correlation between TDP-43 pathology and neuro-inflammation.
Funder Acknowledgement(s): The following work was supported by: Delaware IDeA Network of Biomedical Research Excellence (INBRE) Pilot Award: NIH-NIGMS: 5P20GM103446, NIH-NIGMS Centers of Biomedical Research Excellence (COBRE): 5P20GM103653, Delaware Economic Development Office Grant from the State of Delaware, and NIH-NIGMS G-RISE: 1T32GM144895-01
Faculty Advisor: Dr. Michael A. Gitcho, mgitcho@desu.edu
Role: The part of the research that was conducted by me was the behavioral experimentation (open field and y-maze), immunohistology and protein analysis.