Kaia Amoah

Participant: PROMISE AGEP Research Symposium

Kaia Marie Amoah

Department: School of Medicine

Institution: University of Maryland Baltimore (UMB)

2018 ABSTRACT

Kynurenic Acid Modulation of Excitatory and Inhibitory Synapses and Implications in the Pathophysiology of Schizophrenia

Kaia Marie Amoah; Minerva Contreras, Robert Schwarcz, Ph.D , Thomas Blanpied, Ph.D, and Aihui Tang, Ph.D; and Thomas Blanpied, Ph.D. University of Maryland School of Medicine, Baltimore, MD

Glutamate is a major excitatory neurotransmitter in the mammalian brain and its dysregulation has been linked to the pathophysiology of neurological and psychiatric diseases such as Schizophrenia. Kynurenic acid (KYNA), a product of tryptophan degradation, naturally exists in the brain and can modulate glutamate function by acting as an antagonist to NMDA-type glutamate receptors and other targets. While we can assume the direct role of KYNA in the pathophysiology of schizophrenia, recent evidence suggests that a shift in the excitatory to inhibitory balance of neural circuitry leads to cognitive deficits related to schizophrenia. Despite its significant role in pathological development, as seen by the presence of KYNA in the cerebrospinal fluid of post mortem patients with Schizophrenia, the effect of KYNA at a cellular level is still not fully understood. In this study, we will analyze the effects of kynurenic acid on the formation and function of brain synapses. We hypothesize that kynurenic acid induces the symptoms of schizophrenia by shifting the balance between excitatory and inhibitory neural circuitry. Cultured rat hippocampal neurons were co-transfected with DNA plasmids expressing GFP and FingR-PSD-95 or FingR-Gephyrin (GPHN) to show the dendritic morphology, excitatory synapses and inhibitory synapses, respectively. Cells were either treated with KYNA 10 M or left untreated as a control. An analysis KYNA treated/untreated cells using a confocal microscopy informs us of the change in the spine density and excitatory/inhibitory synapse density upon exposure to KYNA. Cells were tested with various treatment variables to determine the optimal conditions at which KYNA shows significant effects at synapses. Using these same conditions, any shifts in the balance between excitatory and inhibitory synapses were determined. Using the results from this study, we can explain how exposure to KYNA can affect the onset of neurological diseases. Furthermore, our conclusions will allow us to determine whether the effects of KYNA are targeted at specific regions of the dendrite.

BIOGRAPHICAL SKETCH

Kaia Amoah is a STAR-PREP research fellow at the University of Maryland School of Medicine. She received her Bachelor’s degree in cellular and molecular biology from Hampton University in the Spring of 2017. Her previous research experiences include work in prostate cancer epidemiology at the Feinstein Institute of Medical Research, Rotavirus replication research at the Virginia Tech Carilion School of Medicine and phylogenetic research of Red Deepsea Crabs at her undergraduate institution. As a STAR-PREP scholar, Kaia is gaining additional skills and preparation she needs to successfully matriculate into an MD/PHD program. She was thrilled to join the Blanpied Lab after hearing about the projects that are underway and not surprisingly, neuroscience has been nothing short of exciting for her. Currently, Kaia is studying the pathophysiology of schizophrenia, and whether excitatory synapses are affected by kynurenic acid, which is known to be elevated in brains of schizophrenic patients. Most recently, she has presented her findings at the 2017Annual Biomedical Research Conference for Minority Students.

GENERAL SUMMARY OF UNDERGRADUATE RESEARCH

Laboratory of Dr. Emanuela Taioli M.D., Ph.D and Alicia McDonald Ph.D — Department of Epidemiology — The Feinstein Institute for Medical Research, Manhasset, New York.

During the summer of 2014, I had the opportunity to spend 10 weeks working under the direction of Dr.’s Emanuela Taoili and Alicia McDonald at the Feinstein Institute for Medical Research. The project that I worked on focused on the racial disparities in prostate cancer and worked to identify specific biomarkers in order to mediate these disparities in diagnoses, treatment and outcomes.

Laboratory of Sarah McDonald Ph.D — Department of Biomedical Sciences and Pathobioloy — Virginia Tech Carilion School of Medicine, Roanoke, Virginia

During the summer of 2015, under the direction of Dr. Sarah McDonald and graduate student Allison McKell, I worked on a project examining how Rotavirus evolves and replicates to control the progression of disease. I conducted a personal research project where I cloned a strain of Rotavirus Po-13 as a GFP Fusion Protein. The results from my work were used to examine the methods of localization and expression of this GFP-Fusion protein in Sa-11 infected cells. I presented my results at the Virginia Tech Symposium at the conclusion of the summer, where I prepared both an oral and poster presentation. I went on to publish a first authored article of my results in the Journal of the Minority Apprentice (January 2016).

Laboratory of Indu Sharma Ph. D –Department of Biological Sciences – Hampton University, Hampton, Virginia

During the 2016-2017 academic year, I worked under principal investigator, Indu Sharma, whose research assesses the microbial communities of Red Deepsea Crabs and how changes in composition or function of these communities affects their survival. Specifically, I worked to examine the role that host genetics plays in the establishment of a core micro-biome. The results from my work can be used to identify the ecological significance of Red Deepsea Crabs while also aiding in stock assessment and fishery stock management.

SELECTED LIST OF PRESENTATIONS AND PUBLICATIONS

Amoah, Kaia. Protein Localization in RNA Viruses. Journal of the Minority Science Apprentice 2016; 9(1):1-2
“Exploring the Phylogenetic Trees of Red Deepsea Crabs”, ERN Conference, Washington, D.C. Spring 2017
“Exploring the Phylogenetic Trees of Red Deepsea Crabs”, Beta Kappa Chi Conference, Baton Rouge, Louisiana. Spring 2017
“Exploring the Phylogenetic Trees of Red Deepsea Crabs”, Hampton University Research Symposium, Hampton, Virginia. Spring 2017
“Kynurenic Acid Modulation of Excitatory and Inhibitory Synapses and Implications in the Pathophysiology of Schizophrenia”, Annual Biomedical Research Conference for Minority Students, Phoenix, Arizona. Fall 2017