Department of
Psychological and Brain Sciences

• Molecular and Systems Neuroscience

• Lipidomics
• Effects of THC on the developing brain
• Novel endogenous lipids involved in thermoregulation

Two fields that I have a passion for are neuroscience and the biochemistry of lipid signaling. My group combines these fields to understand how lipid signaling drives changes in all aspects of neurophysiology through a systems neuroscience approach. One lipid signaling system currently being investigated centers on endogenous cannabinoids. Cannabinoids are lipids from the plant Cannabis, also known as marijuana.

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 endocannabinoid analogs are produced 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 amides 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.

What are they doing in the brain and body?! Well… that’s what we are in the process of finding out. One of our primary techniques we use in order to study these endogenous lipids is through mass spectrometry. The picture at the top of the page shows a partial view of the internal core of one of the tandem mass spectrometers we have used in our studies over the years. Combining an expertise in lipid mass spectrometry and neuroscience is a powerful combination that allows us to work with collaborators from around the world and to ultimately come to new and exciting discoveries about the field of lipid neuroscience.

A more complete list can be found here

• Leishman E, Cornett B, Spork K, Straiker A, Mackie, K, and Bradshaw HB. Broad impact of deleting endogenous cannabinoid hydrolyzing enzymes and the cannabinoid receptor CB1 on the endogenous cannabinoid-related lipidome in eight regions of the mouse brain. Pharmacol Res. 2016 Apr 22. pii: S1043-6618(16)30344-9. doi: 10.1016/j.phrs.2016.04.020. [Epub ahead of print]PMID: 27109320
• Leishman, E, Mackie, K, Luguet S, and Bradshaw HB. Lipidomics profile of a NAPE-PLD KO mouse provides evidence of a broader role of this enzyme in lipid metabolism in the brain. Biochim Biophys Acta. 2016 Jun;1861(6):491-500. doi: 10.1016/j.bbalip.2016.03.003. Epub 2016 Mar 5.PMID: 26956082
• Smoum R, Bar A, Tan B, Milman G, Attar-Namdar M, Ofek O, Stuart JM, Tam J, Kram V, O’Dell D, Walker MJ, Bradshaw HB, Bab I, Mechoulam R. Oleoyl serine, an endogenous N-acyl amide, modulates bone remodeling and mass. Proc Natl Acad Sci U S A 2010 Oct 12
• Tortoriello G, Rhodes BP, Takacs SM, Stuart JM, Basnet A, Harkney T, Bradshaw HB. Targeted Lipidomics in Drosophila melanogaster Identifies Novel 2-Monoacylglycerols and N-acyl Amides. 2013 PLoS ONE 8(7): e67865. doi:10.1371/journal.pone.0067865
• Raboune S, Stuart JM, Leishman E, Takacs SM, Rhodes B, Basnet A, Jameyfield E, McHugh D, Widlanski T, Bradshaw HB. Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation. Front Cell Neurosci. 2014 Aug 1;8:195. doi: 10.3389/fncel.2014.00195. eCollection 2014
• McHugh D, Hu S S-J, Rimmerman N, Vogil Z., Walker JM, Bradshaw HB. N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor. BMC Neurosci 2010 Mar 26;11:44
• McHugh D, Page J, Dunn E, Bradshaw HB. Δ(9) -THC and N-arachidonoyl glycine are full agonists at GPR18 and cause migration in the human endometrial cell line, HEC-1B. Br J Pharmacol 2012 Apr;165(8):2414-24. doi: 10.1111/j.1476-5381.2011.01497.x. PMID: 21595653.