DOI
https://doi.org/10.25772/J3ZX-2M77
Defense Date
2022
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Sandeep Singh
Second Advisor
Carmen Sato-Bigbee
Third Advisor
Melissa McGinn
Abstract
Our CNS is comprised of billions of neurons and glial cells. Astrocytes are major glial cells and regulate CNS development and functions by providing metabolic, tropic, trophic, and synaptogenic signals to neurons and modulating the blood-brain barrier, oligodendrocyte development, and microglia functions. It is well established that neuron-glia communication is crucial for normal brain development and is altered in many neurological and psychological diseases. Although much progress has been made in understanding how glial cells modulate neuronal functions in the CNS, the precise mechanisms of neuron-astrocyte communication remains less explored. Our lab has shown that a specific sphingolipid, sphingosine-1-phosphate (S1P), and its receptor S1PR1 modulate astrocyte-neuron cross communications in vitro. S1PR1 is specifically and highly expressed in astrocytes and correlates with astrocyte maturation and the synaptogenic period in the developing rodent brain. Our lab also showed that S1P stimulates the expression of astrocyte synaptogenic factors SPARCL1 and TSP4 in a neuronal contact-dependent manner via astrocytic S1PR1 in vitro. However, in vivo role of astrocytic S1PR1 during the developing brain remained untouched. In this thesis, I investigated some of the roles S1PR1 has in astrocytic development in vivo. Specifically, we investigated the role of S1PR1 in BBB integrity, astrocyte volume, surface area, and morphological complexity. Overall, we found that astrocytic S1PR1 does not affect BBB functionality, female astrocytes are larger than male astrocytes, knocking out astrocytic S1PR1 increases GFAP expression, S1PR1 affects astrocytic size in L2-3 female astrocytes, and L4-5 female astrocytes are more complex than their male counterparts.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-10-2022