Frontiers in Cellular Neuroscience (Nov 2021)
Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice
- Haley A. Vecchiarelli,
- Haley A. Vecchiarelli,
- Haley A. Vecchiarelli,
- Robert J. Aukema,
- Robert J. Aukema,
- Robert J. Aukema,
- Catherine Hume,
- Catherine Hume,
- Catherine Hume,
- Catherine Hume,
- Vincent Chiang,
- Vincent Chiang,
- Vincent Chiang,
- Vincent Chiang,
- Maria Morena,
- Maria Morena,
- Maria Morena,
- Maria Morena,
- Catherine M. Keenan,
- Catherine M. Keenan,
- Catherine M. Keenan,
- Andrei S. Nastase,
- Andrei S. Nastase,
- Andrei S. Nastase,
- Francis S. Lee,
- Quentin J. Pittman,
- Quentin J. Pittman,
- Quentin J. Pittman,
- Quentin J. Pittman,
- Keith A. Sharkey,
- Keith A. Sharkey,
- Keith A. Sharkey,
- Matthew N. Hill,
- Matthew N. Hill,
- Matthew N. Hill,
- Matthew N. Hill
Affiliations
- Haley A. Vecchiarelli
- Neuroscience Graduate Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Haley A. Vecchiarelli
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Haley A. Vecchiarelli
- Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Robert J. Aukema
- Neuroscience Graduate Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Robert J. Aukema
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Robert J. Aukema
- Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Catherine Hume
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Catherine Hume
- Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Catherine Hume
- Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Catherine Hume
- Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Vincent Chiang
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Vincent Chiang
- Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Vincent Chiang
- Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Vincent Chiang
- Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Maria Morena
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Maria Morena
- Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Maria Morena
- Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Maria Morena
- Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Catherine M. Keenan
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Catherine M. Keenan
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Catherine M. Keenan
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Andrei S. Nastase
- Neuroscience Graduate Program, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Andrei S. Nastase
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Andrei S. Nastase
- Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Francis S. Lee
- Department of Psychiatry, Weill Cornell Medical College, New York, NY, United States
- Quentin J. Pittman
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Quentin J. Pittman
- Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Quentin J. Pittman
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Quentin J. Pittman
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Keith A. Sharkey
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Keith A. Sharkey
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Keith A. Sharkey
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Matthew N. Hill
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Matthew N. Hill
- Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Matthew N. Hill
- Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Matthew N. Hill
- Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- DOI
- https://doi.org/10.3389/fncel.2021.764706
- Journal volume & issue
-
Vol. 15
Abstract
Cannabinoids, including cannabis derived phytocannabinoids and endogenous cannabinoids (endocannabinoids), are typically considered anti-inflammatory. One such endocannabinoid is N-arachidonoylethanolamine (anandamide, AEA), which is metabolized by fatty acid amide hydrolase (FAAH). In humans, there is a loss of function single nucleotide polymorphism (SNP) in the FAAH gene (C385A, rs324420), that leads to increases in the levels of AEA. Using a mouse model with this SNP, we investigated how this SNP affects inflammation in a model of inflammatory bowel disease. We administered 2,4,6-trinitrobenzene sulfonic acid (TNBS) intracolonically, to adult male FAAH SNP mice and examined colonic macroscopic tissue damage and myeloperoxidase activity, as well as levels of plasma and amygdalar cytokines and chemokines 3 days after administration, at the peak of colitis. We found that mice possessing the loss of function alleles (AC and AA), displayed no differences in colonic damage or myeloperoxidase activity compared to mice with wild type alleles (CC). In contrast, in plasma, colitis-induced increases in interleukin (IL)-2, leukemia inhibitory factor (LIF), monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF) were reduced in animals with an A allele. A similar pattern was observed in the amygdala for granulocyte colony stimulating factor (G-CSF) and MCP-1. In the amygdala, the mutant A allele led to lower levels of IL-1α, IL-9, macrophage inflammatory protein (MIP)-1β, and MIP-2 independent of colitis—providing additional understanding of how FAAH may serve as a regulator of inflammatory responses in the brain. Together, these data provide insights into how FAAH regulates inflammatory processes in disease.
Keywords
