2023 Alzheimer's Association Research Grant (AARG)
Role of Sulfide Pathways and Cannabinoid Type 2 Receptors in Aging and AD
What is the role of the cannabinoid system in Alzheimer’s-related brain inflammation?
Kevin Murnane, Ph.D.
LSU Health Sciences Center, Shreveport
Shreveport, LA - United States
Background
Aging is one of the largest risk factors for Alzheimer’s. Several biological mechanisms may contribute to the risk associated with aging. One is called “inflammaging,” which is a low level of long-term inflammation throughout the brain and body during the aging process.
Researchers are investigating the role of a nerve pathway in the brain known as the endocannabinoid system which includes nerve cells that respond to a class of drugs known as cannabinoids. Cannabinoids can come from external sources (such as cannabis) or from naturally occurring molecules in the brain (endocannabinoids). Several studies have shown that activation of the endocannabinoid system in the brain can reduce inflammation and potentially reduce damage to nerve cells.
One mechanism for activating the endocannabinoid system is a receptor or “docking site” on the surface of brain cells called the cannabinoid type 2 (CB2) receptor. CB2 appears to be involved in how the endocannabinoid system responds to and impacts immune function. However, how endocannabinoid activation may lead to anti-inflammatory effects in the brain in aging and Alzheimer’s is still not well understood.
Research Plan
Dr. Kevin Murnane and colleagues will study how a molecule called hydrogen sulfide may stimulate CB2 receptors to impact Alzheimer’s-related brain inflammation and cognitive decline in genetically engineered Alzheimer’s-like mice. The researchers will give the mice one of two substances that activate CB2 receptors: a drug made in the laboratory or a naturally occurring and FDA-approved food additive (BCP). Dr. Murnane and team will assess the cognitive function of the mice with behavioral tests and then study their brains for evidence of inflammation.
Finally, Dr. Murnane and colleagues will study if the addition of cannabidiol (CBD) to either drug treatment is more effective in improving cognition or brain inflammation in genetically engineered Alzheimer’s-like mice. After treatment, the researchers will again study the behavior and brains of the mice for signs of cognitive decline, inflammation, and levels of sulfides.
Impact
The findings may contribute to the understanding of the role of the endocannabinoid system in aging and Alzheimer’s. If successful, the results may suggest novel targets for the development of therapeutics for Alzheimer’s.