Defense Date

2021

Document Type

Thesis

Degree Name

Master of Science

Department

Anatomy & Neurobiology

First Advisor

Jeffrey L. Dupree, Ph.D.

Second Advisor

John Bigbee, Ph.D.

Third Advisor

Carmen Sato-Bigbee, Ph.D.

Abstract

The axon initial segment (AIS), an axonal sub compartment located immediately distal to the soma, is an important structure in mediating action potential generation and modulation. The morphology of this domain can be altered by a wide variety of activity-dependent, environmental, and pathological triggers. Dysregulation of axonal calcium (Ca2+) concentrations, and subsequent enzymatic degradation of AIS cytoskeletal architecture have been reported to underlie structural modifications of the AIS. Moreover, pharmacological inhibition of neuronal Ca2+ channels have been shown to mitigate the disruptive effects of neuroinflammation on AIS structural integrity. Here we investigate the Cisternal Organelle (CO), a specialized subsection of endoplasmic reticulum and putative Ca2+ regulator localized within the AIS. Although poorly understood, CO integrity has been shown to be crucial for AIS maintenance, and vice versa. With this in mind, we proposed that pathological insult to the AIS would be accompanied by CO disruption. To test this hypothesis, we induced experimental autoimmune encephalomyelitis (EAE) in mice and immunohistochemically labeled against the AIS and CO markers. Using laser scanning confocal microscopy, and three-dimensional image analysis software, we quantitatively compared morphological characteristics AIS and CO between treatment groups. Interestingly, we reveal pathologically induced alterations in CO structure in parallel with AIS disruption. Corresponding alterations in CO integrity may indicate homeostatic functionality, however further investigation is required to elucidate its functional significance. Overall, our findings identify a novel response to neuronal insult and may provide insight into new therapeutic targets in a variety of CNS pathologies.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-13-2021

Available for download on Tuesday, May 12, 2026

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