2019 Winner: Significance of NRROS in CNS Homeostasis

Project Information
Significance of NRROS in CNS Homeostasis
BME 195 (Bioengineering Independent Thesis)
Negative regulator for reactive oxygen species, also known as NRROS, is a protein that is highly expressed in the endoplasmic reticulum of immune cells with phagocytic capabilities. NRROS is responsible for regulating the production of reactive oxygen species (ROS) during inflammatory responses. The role of NRROS is crucial in preventing collateral tissue damage because ROS are highly reactive chemical species that adversely alter all macromolecules, hence being toxic for your cells. Recent studies have shown that the deletion of NRROS in mice leads to spontaneous neurological disorders and ultimately early mortality at 6 months of age.
The goal of this research project was to observe and describe the neurological defects associated with the absence of NRROS in the central nervous system (CNS) of mice, with the aim of figuring out what defect causes early mortality in these mice. The implementation of the cre-lox recombinase system allowed for NRROS to be partially expressed (heterozygous) or fully absent (mutant) in the CNS myeloid cells of mice. To analyze the deleterious effects of an NRROS-deficient environment on the CNS, I extracted and sectioned the brains of heterozygous mice and mutant mice, conducted immunohistochemistry stainings that targeted specific neuroglia cells, and conducted a comparative analysis between the heterozygous and mutant brains. Results confirmed the presence of astrogliosis, a hallmark of neurodegenerative diseases. Also, data from the mutant antibody stainings displayed that there is a complete loss of steady state and activated microglia cells, which are the brain tissue-resident immune cell, and instead an emergence of an activated immune cell described as PLC macrophages. The loss of microglia and the presence of PLCs indicates that NRROS plays a cell-intrinsic role in microglia development. Additionally, the neurological disorders resulting from NRROS deficiencies in mice demonstrates the crucial role NRROS plays in brain homeostasis and healthy CNS development.
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  • Amr Khalid Makhamreh (Ten)