Date Approved

8-2020

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology

Department

Cell Biology and Neuroscience

College

Graduate School of Biomedical Sciences

First Advisor

Venkataswar Venkataraman, PhD

Committee Member 1

Robert Nagele, PhD

Committee Member 2

Nimish Acharya, PhD

Committee Member 3

Mikhail Anikin, PhD

Committee Member 4

Daniel Chandler, PhD

Subject(s)

Neuronal Calcium-Sensor Proteins, Hippocalcin, Neurocalcin, Cell Body, Neurodegenerative Diseases, Calcium-Binding Proteins

Disciplines

Cell Biology | Medical Cell Biology | Medical Molecular Biology | Medical Neurobiology | Medicine and Health Sciences | Molecular and Cellular Neuroscience | Molecular Biology | Nervous System Diseases

Abstract

Calcium signaling is particularly important for neuronal function. Neurons utilize a wide range of calcium-binding proteins. Dysregulation of such proteins is linked to neurodegeneration. Neurocalcin delta (NCALD), hippocalcin (HPCA), and S100B are calcium sensors that are expressed in the hippocampus, a brain region essential to memory and severely damaged in Alzheimer’s disease (AD). Despite the potential importance of these proteins, we do not fully understand the physiological significance of their relationship. Because NCALD and HPCA are known to interact with S100B, we hypothesized that the loss of S100B affects NCALD and HPCA localization, and therefore electrical properties, of hippocampal neurons. When we compared S100B knockout and wild-type mice via immunohistochemical analyses, we observed possible changes in localization of both proteins, particularly in CA1, and a change in the NCALD to HPCA ratio in cell body layers of the DG, CA2, and CA3 regions. Given that protein localization is critical for proper functioning, it is possible that these changes impact electrical properties of neurons. Electrophysiology data suggested an increase in intrinsic excitability in the DG, but a decrease in CA1 when S100B was deleted. The extent to which NCALD, HPCA, and S100B are involved in determining membrane properties, and their interrelationship, remain to be elucidated. Our results have provided foundational data that supports the hypothesis and is likely to lead to a greater mechanistic understanding of calcium signaling in the hippocampus in future studies. Delineating the relationships between calcium-binding proteins could reveal previously unknown facets of neurodegenerative disease pathology.

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