Brain-immune Interactions in Neurodegenerative Disease (2014-2015)
Understanding how the immune system in the brain responds to disease remains a frontier of science and is of fundamental importance. We are particularly interested in chronic brain disease such as Alzheimer’s disease (AD). Multiple studies now show that specific immune-system-related genes are not only associated with increased risk for AD, but also are part of its neuropathologic mechanism. Despite these exciting findings, we still don’t understand how immune cells such as microglia are involved in the initiation of the disease process, how their involvement changes over time or what type of response is generated by microglia at different stages of AD. The faculty leads’ lab discovered that one mechanism by which microglia control the microenvironment in the brain is via nutrient deprivation, that is, by lowering brain levels of the critical amino acids arginine and tryptophan. Tryptophan, in particular, plays an important role in both memory and in affective disorders such as depression.
This project team examined how immune activation of microglia alters levels of arginine and tryptophan in the environment and how these changes impact brain function to induce pathology using cell culture and genetically altered mice. Team members had the opportunity to attend the FASEB Neuroimmunology meeting July 13-18 in Big Sky, Montana, and the course on Introduction to Neuroimmunology offered prior to the meeting.
The core program focused on bench sciences. Scientific literacy and lab exercises enabled the trainee students to develop their individual research questions, design strategies and choose methods to address the question of how the immune system in the brain responds to chronic disease. Students in all three participating labs mastered a variety of lab techniques and acquired skills and tools required for designing a research study.
All student team members took an independent study for the fall semester to work on their individual research projects, and are continuing in the spring semester. In addition to the regular team meetings, invited speakers presented the bedside aspect of Alzheimer’s disease and spoke with the students about their clinical experiences with AD patients.
Summer 2014 – Spring 2015
Arginine Deprivation and Immune Suppression in a Mouse Model of Alzheimer’s Disease. Matthew J. Kan, Jennifer E. Lee, Joan G. Wilson, Angela L. Everhart, Candice M. Brown, Andrew N. Hoofnagle, Marilyn Jansen, Michael P. Vitek, Michael D. Gunn, and Carol A. Colton. The Journal of Neuroscience, 15 April 2015, 35(15):5969-5982.
White Matter Alterations and Methionine Cycle Dysregulations in Mouse Models of Alzheimer’s Disease (poster by Lauren Kane, Alexandra Badea, Joan Wilson, Angela Everhart, Yi Qi, G. Allan Johnson, Carol A. Colton)
White Matter Alterations in Mouse Models of Alzheimer’s Disease (poster by Lauren Kane, Alexandra Badea, Angela Everhart, Joan Wilson, Yi Qi, Allan Johnson, Carol Colton)
Tom40 and the mt(UPR) (presentation by Sonal Gagrani)
This Team in the News
See related team, Brain-immune Interactions in Neurodegenerative Disease (2015-2016).
/faculty/staff Team Members
Ornit Chiba-Falek, School of Medicine-Medicine: Neurology
Carol Colton, School of Medicine-Medicine: Neurology*
William Gottschalk, School of Medicine-Medicine: Neurology*
Michael Gunn, School of Medicine-Medicine: Cardiology*
/undergraduate Team Members
Alison Chan, Neuroscience (BS)
Sonal Gagrani, Neuroscience (BS)
Lauren Kane, Neuroscience (BS)