“ Why Italy?” everyone asked me when they found out that I had just received a BRAVO! grant to do research in the foreign country. “Seriously? Why NOT Italy,” was my response. Who wouldn’t want to spend four months in Florence, the art and beauty capital of the world? My plan was to do research on Alzheimer’s disease under the supervision of Dr. Giancarlo Pepeu, Head of the Neuropharmacology Unit in the Medical School of the University of Florence. My research advisor at the University of Arizona, Dr. Carol Barnes, Neural Systems, Memory and Aging (NSMA), had corresponded with the Florence lab in the past. I was thrilled to be given the opportunity to perform a drug study and discover a direct application of Alzheimer’s research.

Okay, so I’m not going to lie and say that I wasn’t scared out of my mind to be living on my own for four months in a foreign country! I barely had a grasp of about 25 words of the Italian language, and this was the first time I had ever been away from home for this long. I must admit, my journey to Italy was probably one of the worst nightmares of my life, and I was this close to jumping on the next plane out of there – and back to my comfort zone… but… I didn’t, and words can’t describe how glad I am that I didn’t. I think I learned more about myself in that four months than I had learned in my entire life.

The Italian culture is vibrant and lively, full of animated gesturing, good-natured arguing, and lots and lots of SMOKING. (I practically had to go into nicotine detox when I got back to the US from inhaling everyone’s second hand smoke!) Making friends was slightly difficult because I had no access to English-speakers, but looking back, I wouldn’t have it any other way. Not surrounding myself with English speakers forced me to learn the language as quickly as possible; and it allowed me to get to know Italy on a more intimate level. Florence, or Firenze in Italian, is one of the most beautiful cities you’ll ever see. I often found myself walking to the bridge, Ponte Vecchio, whenever I had a spare moment, to gaze at the surroundings in awe. I also made it a point to travel every weekend. I was never without my guidebook, and each week I would turn to a different section so I could research the place I would travel next. While weekends were spent as an independent explorer, weekdays were spent working hard and laughing hard in the lab with my new Italian “family.” “Le mie ragazze,” as I called them, were such a delightful and caring group of people. From day one, they made me feel comfortable and appreciated. Often, I was welcomed into their homes to eat delicious, but MASSIVE, meals with their families. Despite the very prominent language barrier, they taught me an abundance of both Italian culture and neuropharmacology.

Alzheimer’s Disease (AD) is a devastating cognitive disorder that affects the elderly. Unfortunately, the complete source of its symptoms is not entirely known. The three main structural changes of an AD brain are a loss of neurons in the hippocampus and neocortex, an accumulation of intracellular filaments made of hyperphosphorylated tau protein (neurofibrillary tangles), and extracellular formation of senile Aß protein plaques. Our interest is in determining the neurological characteristics of a transgenic animal model of AD. TgCRND8 mice display spatial learning deficits, along with an increased level of soluble Aß and Aß-containing plaques. Our primary goals were: to explore the relationship between Aß deposition and forebrain cholinergic dysfunction; characterize the progression of Aß deposition-induced molecular alterations, and to evaluate the effectiveness of a new drug using metal chelation therapy. Our first task was to establish a characterization of the Aß plaques and neurochemical alterations in both Tg and non-Tg mice. We evaluated neurotransmitter release, particularly Ach, GABA, and glutamate, by means of microdialysis, and found that there was a significant loss of cholinergic function in the cortical and/or hippocampal systems. We also performed behavioral tests to determine whether there were cognitive deficits in the TgCRND8 mice. We found that cognitive impairment was present at around 5 months of age.

After characterizing the TgCRND8 mice, we began drug treatment with Clioquinol, a metal chelator. Past studies have shown that Cu/Zn metal chelators, like Clioquinol, can solubilize the toxic insoluble form of Aß and possibly decrease Aß deposition in the AD brain. We performed microdialysis to determine Clioquinol’s effect on the cholinergic system, Immunohistochemistry, and behavioral studies. Although we did not entirely finish our project, we did receive several data, which I will be processing and corresponding with my Florence team.

Looking back on my time in Italy almost seems like a dream. I made friends from around the world and I am positive that I will someday return. (I’m even studying the language now!). I learned to find commonalities in cultures that appear so unfamiliar. I realized subtle differences in the approach to research across the globe. And I developed a new appreciation for the importance of foreign scientific collaboration. If you have ever considered the possibility of going abroad, but wonder if it’s for you, my advice is to not hesitate for a moment. The experience will change your life, and if you’re like me, it will be something you will never forget.

I would like to extend a deep gratitude to everyone who supported me in my research and travels. My thanks go to Carol Bender, Genevieve Kenney, and the BRAVO! program for making this possible. I am also eternally indebted to Dr. Fiorella Casamenti, Dr. Giancarlo Pepeu, Dr. Carol Barnes, and all of my irreplaceable lab mates in Italy!

Brynne Crowell, UBRPer in Dr. Carol Barnes’ lab, Neuroscience: Neural Systems, Memory and Aging.