IARS 2026 International Outreach Travel Grant Interview: Antonello Penna Silva, MD, PhD

Altered Microglial–GABAergic Interactions and Npas4 Expression Are Associated with Stage-Dependent Changes in Propofol Sensitivity in 5XFAD Mice

Abstract Presentation:

Kosaka Best Abstract Awards Session on Sunday, May 3, 2026, 7:00 am – 8:30 am, in Av. Laurier, Convention Level at the Fairmont The Queen Elizabeth, during the 2026 Annual Meeting, Presented by IARS and SOCCA

Throughout his research career, Antonello Penna Silva, MD, PhD has been dedicated to uncovering the intricacies of neurophysiological vulnerability of older adults to anesthesia and the role it plays in postoperative cognitive decline. Initially, his investigations focused on the basic molecular mechanisms of GABAergic modulation but have since progressed to a multidisciplinary approach that integrates mechanistic neuroscience with clinical outcomes, specifically investigating how neuroinflammation and synaptic homeostasis influence anesthetic pharmacodynamics in the aging brain. An anesthesiologist and associate professor at the Facultad de Medicina y Hospital Clínico de la Universidad de Chile in Santiago, Chile, Dr. Penna Silva and his research team have made great strides in better understanding this condition in older adults. Recognized as an IARS 2026 International Outreach Travel Grant and a Kosaka Basic Research Finalist, Dr. Penna Silva’s current research project, “Altered Microglial–GABAergic Interactions and Npas4 Expression Are Associated with Stage-Dependent Changes in Propofol Sensitivity in 5XFAD Mice,” aims to determine whether Alzheimer’s disease (AD) mouse models at different stages, early versus late, exhibit uniform susceptibility to the effects of propofol. During the Kosaka Best Abstracts Session on Sunday, May 3, at the 2026 Annual Meeting, presented by IARS and SOCCA, he will share how they have discovered a biphasic response in which early-stage mice unexpectedly showed resistance to the anesthetic. The next step will be to identify the underlying molecular mechanisms. Below, Dr. Penna Silva discusses the evolution of his research, what he will gain by attending the IARS Annual Meeting and how this travel grant will impact the future of his career and investigations into this important topic.

1. For this research, you are…

Principal Investigator

2. What drew you to this area of research? Has it evolved since your initial research project?

My research is driven by a desire to understand the neurophysiological vulnerability of older adults to anesthesia and its role in postoperative cognitive decline. While my earlier work focused on the basic molecular mechanisms of GABAergic modulation, my focus has evolved into a multidisciplinary approach that integrates mechanistic neuroscience with clinical outcomes, specifically investigating how neuroinflammation and synaptic homeostasis influence anesthetic pharmacodynamics in the aging brain.

3. What are the goals you most want to accomplish in your work with this research project (or projects)?

The primary goal of this project was to determine whether Alzheimer’s disease (AD) mouse models at different stages—early versus late—exhibited uniform susceptibility to the effects of propofol. Having discovered a biphasic response in which early-stage mice unexpectedly showed resistance to the anesthetic, we are now focused on identifying the underlying molecular mechanisms. Specifically, we aim to understand how Npas4 downregulation and altered microglial-GABAergic interactions drive these stage-dependent shifts in sensitivity.

4. What is the potential impact of your research on the field of anesthesia and patient care?

This research establishes for the first time that patients in the early stages of Alzheimer’s may actually be more resistant to general anesthetics like propofol, while those in advanced stages show hypersensitivity. These findings suggest that we cannot assume a “one-size-fits-all” approach to anesthetic vulnerability in cognitive impairment. It highlights the critical need to personalize anesthetic dosing, a goal that is currently achievable through the use of processed EEG monitors to track brain activity in real-time.

5. How do you feel about receiving the IARS International Outreach Travel Grant?

I am deeply grateful to the IARS for this opportunity. The IARS Annual Meeting is unique because it consistently showcases “frontier research” at the leading edge of anesthesiology. Being recognized with this grant is a privilege, as it allows me to participate in a forum that prioritizes the same scientific rigor and innovation that I strive for in my own laboratory.

6. How will this grant affect your research and professional trajectory?

This grant is essential to my professional trajectory, as it provides the means to establish international collaboration networks, which are vital to the growth of our research group in Chile. It will help me bridge the gap between our preclinical findings and clinical application, accelerating my goal of becoming a leader in the field of perioperative neurocognition.

7. What are the benefits of presenting your research at the IARS Annual Meeting?

The Annual Meeting offers an unparalleled opportunity to receive high-level feedback to optimize this specific project. Presenting to a global audience of experts is the most effective way to validate our results, refine our experimental approaches, and build the professional collaborations necessary to scale our research.

8. Is there anyone else you wish to acknowledge as part of this research team?

I would like to acknowledge the multidisciplinary team at the Universidad de Chile and the Hospital Clínico, particularly my co-authors Pedro Lobos, Jamileth More, Barbara Bruna, Rodrigo Gutiérrez, and José Egaña, whose dedication made this work possible.

9. Outside of your research, what might someone be surprised to learn about you?

I have a deep passion for taking on new challenges and staying active through sports, particularly basketball. I also find great inspiration in the diverse natural beauty of my home country, Chile—from trekking through the mountains and deserts to exploring the rugged coastlines and glaciers.