DOI
https://doi.org/10.25772/T74E-K326
Defense Date
2023
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Dr. Sandeep Singh
Second Advisor
Dr. Kelly Harrell
Third Advisor
Dr. Carmen Sato-Bigbee
Abstract
Astrocytes are the most abundant cell type in the mammalian brain performing a multitude of critical functions in the central nervous system such as regulating ion homeostasis, providing metabolic and trophic support, and controlling synapse formation and plasticity. Astrocyte function is imparted by their structural complexity in which processes extend and ramify throughout the brain parenchyma and interact with many cell types. However, the mechanisms that regulate the proper differentiation and structural development of astrocytes and their processes remain elusive. Our lab has shown in vitro that the G-protein coupled receptor, S1PR1, regulates astrocyte morphogenesis in a neuron-astrocyte contact dependent manner. In vivo however, this hypothesis has yet to be tested. In this thesis, we attempted to understand the role of S1PR1 in astrocyte morphogenesis in vivo through the genetic ablation of astrocytic S1PR1 in a mouse model. We sparsely labeled cortical astrocytes in layers 2-3 and 4-5 of the somatosensory cortex by injecting an astrocyte-specific transgene expressing green fluorescent protein and further quantified morphometric parameters such as surface area, volume, and complexity across different subcellular regions by using the 3D-reconstruction software IMARIS. Overall, we found sex-based and region-specific differences in gross and subcellular morphology between WT and S1PR1ΔAst. cortical astrocytes, predominantly in the deeper layers of the cortex in our male cohort.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-5-2023
Included in
Biochemistry Commons, Developmental Neuroscience Commons, Medicine and Health Sciences Commons