The two fields that I have a passion for are the neuroscience of reproduction and the biochemistry of lipid signaling. My group combines these fields to understand how lipid signaling drives changes in reproductive neurophysiology through a systems neuroscience approach. One lipid signaling system currently being investigated centers on endogenous cannabinoids. Cannabinoids are the active compounds in the plant cannabis (pictured to the right).
Cannabinoid compounds activate receptors throughout the body and the nervous system and regulate a myriad of neurophysiological pathways. These receptors did not evolve to prepare for the likelihood that an organism would someday ingest compounds from a cannabis plant. They evolved in concert with endogenous signaling molecules that are collectively called endocannabinoids. The most studied of these are the lipid signaling molecules, Anandamide and 2-arachidonoyl glycerol. However, there is growing evidence that these two lipids are not alone in exerting cannabimimetic (cannabinoid-like) effects in the body. Many of these novel endogenous endocannabinoid analogs are produced in the female reproductive tract and throughout the nervous system.
Interestingly, Anandamide is arguably the world’s most famous molecule in a very specific class of molecules structurally referred to as N-acyl amides. While it is true that N-acyl amide are not yet particularly well known throughout scientific communities, we will argue that they are quite well known throughout all of the plant and animal kingdoms in that they are ubiquitous molecules that are formed from simple fatty acids and amines and are likely present in most-if not all-forms of life. This presence provides an opportunistic situation for them to be used as signaling molecules and as metabolic precursors to additional signaling molecules. How they are synthesized, metabolized, and what they do in each of these systems is largely unknown. Given their ubiquitous nature, it is actually a narrow view that they are most specifically endogenous cannabinoids; however, it is the case that our understanding of their signaling properties currently stems from the work of how some are endogenous counterparts to the wide range of cannabis plant lipids that activate both GPCR and ion channels.
What are they doing in the brain and body?! Well… that’s what we are in the process of finding out. Of particular interest to my group is their involvement in the neurophysiology of pelvic pain. Lipid signaling molecules have a long history of being involved in pain and inflammation. NSAIDs (non-steroidal anti-inflammatory drugs) such as aspirin and ibuprofen (Advil) block the production of the lipid signaling molecules from the family called Prostaglandins. Prostaglandins, like endocannabinoids, are made with the fatty acid, arachidonic acid and so share structural similarity. We have multiple lines of research ongoing that will lead us to a greater understanding of the following: 1) the biochemical role of endogenous cannabinoids in regulating cell migration of endometrium within the reproductive tract and how this communication plays a role in the pelvic pain disorder, endometriosis, 2) how steroid hormones regulate the production and activity of these lipid signaling molecules, 3) how the biochemistry and neurophysiology of this family of lipids acting as cellular signals drive cell-cell communication, and 4) how the biochemistry of lipid biosynthesis and metabolism of the class of lipids called "N-acyl amides" shapes the lipidome of the entire CNS, which ultimately drive behavior.