Degree Type

Honors Capstone Project

Date of Submission

Spring 5-9-2020

Capstone Advisor

Sandra J. Hewett

Honors Reader

Jessica MacDonald

Capstone Major

Biology

Capstone College

Arts and Science

Audio/Visual Component

no

Keywords

astrocyte, system xc-, neuron, morphology, brain morphology, cystine, glutamate, glutathione, cortex, cerebral hemisphere, corpus callosum, hippocampus, lateral ventricles, striatum

Capstone Prize Winner

no

Won Capstone Funding

no

Honors Categories

Social Sciences

Subject Categories

Biology | Cell and Developmental Biology | Developmental Biology | Developmental Neuroscience | Neuroscience and Neurobiology

Abstract

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from male and female mice and gross morphological measurements over the rostro-caudal extent of each brain were made of the cerebral hemispheres, cortex, hippocampus, striatum, lateral ventricles, and corpus callosum. The following sex and genotype differences were observed. In female mice, corpus callosal area in AcKO mice was significantly larger and lateral ventricular area significantly smaller than sex- matched wild-type littermate controls. In males, lateral ventricular area was also smaller in AcKO mice and this occurred in association with a significantly larger striatal area than sex- matched littermate controls. Both male and female AcKO mice had larger hippocampal areas than their wild-type controls in the most rostral section of tissue only. All abnormalities observed indicate the importance of system xc-, in general, and astrocyte system xc-, in particular, to construction of proper brain morphology.

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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