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

Available for download on Wednesday, May 03, 2028

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