Sexual Dimorphism in Gut-Brain Signaling
Abstract
There is a growing consensus of the importance of the gut-brain axis, including the gut microbiome, for influencing health and cognitive functions. Intestinal cells, like neurons, have their own intrinsic chromosomally-based sexual identity, which must be actively maintained in adults suggesting intestinal cells can function differently whether they are male or female. Enteroendocrine cells (EE), which function as specialized chemosensory cells located within the the Drosophila intestinal epithelium, exhibit sexually dimorphic changes in gene expression including genes which encode neurotransmitter receptors. In this proposal, we investigate how intestinal cellular sex impacts gut-brain communication and behavior by identifying sexually dimorphic: 1) variations in adrenergic and glutamatergic receptor expression, 2) brain neurons that receive aggression-promoting gut signals, and 3) transcriptome and behavioral responses to stress and bacterial metabolites. To achieve our objectives, we are using genetic approaches to interfere with specific adrenergic receptor functions via genome editing and genetically encoded tools such as thermo/optogenetics to interfere with EE and activity. We are assessing the consequences at the level of molecules (transcriptomics), cell activity (Ca2+ imaging), and whole animal (behavioral assays). A greater understanding of sexual dimorphism in the levels and transcript usage of receptors that mediate intestinal cell and neuronal activity will help map the internal codes of social behavior and dynamics as well as reveal therapeutic targets that could modulate aggression.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 22, 2022
- Source ID
- W911NF2310005
Entities
People
- Sarah Certel
Organizations
- Army Contracting Command
- United States Army
- University of Montana