Tetrahydroisoquinoline Neurotoxins and Parkinson Disease

iii DEDICATION To my loving wife, best friend and eternal companion Norma. With love and thanks for supporting me in all my endeavors into neuroscience and neurosurgery. You make my journey worthwhile. iv ACKNOWLEDGEMENTS First and foremost, I would like to thank my research advisor and mentor, Dr. Mark LeDoux, for the training I received in his laboratory. His encouragement, advice and supervision in my research and medical endeavors are much appreciated. Of utmost importance to my career, I appreciate his time, effort and motivation in my education on scientific writing. I would like to thank the members of my graduate committee, Drs. for their valuable comments and advice on my qualifying exam, research proposal and dissertation formulation. I would also like to sincerely thank all the current and former members in Dr. for their technical assistance, suggestions and camaraderie. In particular, I would like to thank Dr. Yu Zhao for her extensive training and assistance in cell culture techniques and valuable input regarding my experiments. Her scientific knowledge and friendship were welcoming and valued in the often-times rough seas of graduate school. During my graduate school training I have had the privilege to learn from several faculty members in the Department of Anatomy and Neurobiology. My sincere thanks to: Drs. neuroscience graduate program director, who provided me with direction and support from the very beginning of my foray in neuroscience. Many thanks to the staff in the Departments of Neurology and Anatomy and Neurobiology, including Brenda Smith for her administrative help in graduate school and Mary Reed, Bobbie Scott, and Frances Grigsby for their help in reagent purchasing and administrative work. I would especially thank my wife and my extended family for their incredible love and support throughout my graduate training. Finally, I would like to thank the National Institute of Neurological Disorders and Stroke for financial support (R03-NS049123 to MSL). v ABSTRACT The goal of this dissertation work was to (1) determine the distribution of several tetrahydroisoquinoline (TIQ) derivatives in rodent, normal human and Parkinson disease (PD) brain, (2) quantify the levels of these TIQ derivatives in common food sources in an effort to link specific food intake patterns with the development of PD and (3) examine the neurotoxicity of select TIQ derivatives in human dopaminergic cell culture. The TIQs are a family of monoamine alkaloids that share structural homology with 1-methyl-4-phenyl-1,2,3,6-tetrahyrdropyridine (MPTP), can be formed from dopamine …