Chronic high blood pressure, also known as hypertension, affects one in every three adults in the United States and nearly 1 billion people worldwide. It has been shown that the hormone, Angiotensin II (ANG-II), acts within the brain to stimulate the sympathetic nervous system, leading to hypertension. A region in the brain that is particularly sensitive to ANG-II and is involved in hypertension is the subfornical organ (SFO). The SFO is connected by neural projections to the paraventricular nucleus of the hypothalamus (PVN), and this pathway has been suggested to be important in cardiovascular regulation. The hypothesis of my study is that endoplasmic reticulum (ER) stress in the SFO-PVN projecting neurons is a cause of ANG-II hypertension. To test my hypothesis, the study will be split into two portions. In the first set of experiments, we will use staining of brain tissue (immunohistochemistry) to evaluate whether infusion of ANG-II causes ER stress in SFO neurons that send projections to the PVN. If we find ER stress in these neurons, we will use genetic approaches (CAV2-Cre-GFP and AAV2-Flex-GRP78) to inhibit ER stress and determine whether this also prevented ANG-II hypertension from developing.
What did you learn working in the lab?
Working in Dr. Young’s lab has been enlightening, exciting, and frustrating at times. There are many skills that take a great deal of practice to master that are required for studies like this one. For example, in order to perform Immunohistochemistry to identify markers of ER stress in the brains—a technique I learned this summer—I first had to learn to use a cryostat to precisely slice and collect the brains onto glass slides. I sliced dozens of practice brains before I mastered the skill and even now after weeks of practice, I still face challenges and make mistakes while performing this task. I also learned skills like suturing, small procedures, injections, bench work, and many others.
I very much enjoy the lab environment. It is great to have such a close-knit team that genuinely wants to help each other succeed. I wasn’t anticipating the level of team work involved in running a research lab, but that is truly the foundation. I would say that the friendships are the best part of working in a lab. The worst part of working in the lab is the waiting. For example, I surgically placed ANG-II osmotic pumps in the mice and then had to wait two weeks before taking the next step in my study. During that time, I practiced on the cryostat a lot, but there was still significant down time that I filled with tasks unrelated to my project such as helping other lab members with their work, cleaning, etc.