"Age-Dependent Breakdown of the Blood Brain Barrier and Associated Chan" by Eric V. Brown

Author(s)

Eric V. Brown

Date Approved

5-2015

Document Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

Department

Cell Biology

College

Graduate School of Biomedical Sciences

First Advisor

Venkataswar Venkataraman, PhD

Committee Member 1

Robert Nagele, PhD

Committee Member 2

Bradford Fischer, PhD

Subject(s)

Autoantibodies; Blood-Brain Barrier; Calcium-Binding Proteins; Neurodegenerative Diseases; Age Factors; Models, Animal

Disciplines

Animal Experimentation and Research | Cell Biology | Disease Modeling | Genetics and Genomics | Laboratory and Basic Science Research | Molecular Biology | Nervous System Diseases | Neuroscience and Neurobiology

Abstract

Autoantibodies play an important role in many autoimmune diseases. Recent research has shown that breakdown of the blood brain barrier (BBB) occurs concomitant to generation of brain reactive autoantibodies in many neurodegenerative diseases, which serve as biomarkers and drivers of pathology. SI00B, a calcium binding protein found most highly expressed in astrocytes which ensheathe the BBB, has many functions in neural development and signaling. Currently literature indicates that S100B KO mice develop normally, with no phenotypic abnormalities. Here, it is demonstrated that S100B KO mice seem to develop a chronic BBB breakdown similar to that seen in human neurodegenerative diseases. The pattern of breakdown remains similar across multiple brain regions and seems to worsen in a predictable way according to mouse age. This chronic deficiency seems to be associated with changes in the brain reactive autoantibody profile of these mice. Current models of chronic BBB breakdown and subsequent autoantibody generation are lacking; Sl00B KO mice show potential for use as a model for this phenomenon.

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