The study is published in the latest March issue of the journal European Molecular Biology Organization.
In the bloodstream, the interaction between the protein receptor CD40 and another protein, CD40 ligand (CD40L), allows white cells to trigger antibody production and to activate cellular immunity. This immune response helps neutralize foreign invaders, such as bacteria and viruses. However, in an earlier study, the USF reseachers found that when this same CD40-CD40L signaling system is triggered in the brain, the immune response can cause microglia damage to neurons.
This latest study demonstrates for the first time that CD40 is produced and displayed on the surface of neurons in the brain. It also attempts to answer the question: What is the purpose of CD40 on neurons?
The researchers came up with two answers. First, they found that adding CD40L to immature neurons caused these primitive cells with few connecting branches to mature into neurons with widespread branches suitable for making connections to other neurons.
Secondly, in the presence of CD40L, neurons with CD40 on their surface were much more likely to resist injury than neurons not given CD40.
What the researchers found in the test tube also was borne out in transgenic mice deficient in CD40. The brains of these older, CD40-deficient mice showed signs of degeneration and the mice demonstrated gross central nervous system abnormalties with age.
"These effects suggest that the CD40 signaling on neurons plays a physiological role in normal neuronal cell maintenance and confers resistance to aging-induced stress," Jun Tan, MD, PhD, of the Roskamp Institute and lead investigator for the study.
The findings suggest that in early life the CD40-CD40L signaling system plays a key role in differentiating immature cells into fully functioning neurons, Dr. Tan said. "In later life, the CD40-CD40L interaction appears to become important as a survival factor — neurons under stress might be rescued by this system."
One practical implication of the research, which requires further study, is that CD40 might be beneficial as a new survival or growth factor for neurons. It may be enlisted to prompt stem cells to differentiate into functioning neurons, or to help protect transplanted cells administered as therapies, said Terrence Town, a co-author of the study.
"It is possible that the CD40-CD40L interaction may be important to promote neuronal growth and survival after head injury, stroke or other central nervous system damage."
Dr. Tan and Terrence Town worked with Michael Mullan, MD, PhD, director of the Roskamp Institute, on the CD40 study. The Roskamp Institute is dedicated to finding treatments for Alzheimer's disease and other neurological disorders.