2023 Alzheimer's Association Research Fellowship (AARF)
Immune Regulation of the Synapse Following TBI in Alzheimer’s Models
How may an immune system protein help increase brain cell dysfunction and Alzheimer’s risk after traumatic brain injury?
Jaclyn Iannucci, Ph.D.
Texas A&M University Health Science Center
College Station, TX - United States
Background
Traumatic brain injury (TBI) results from an injury to the head that disrupts normal cognition (brain function). Studies suggest that individuals who experience cognitive loss after TBI may have an increased risk of Alzheimer’s and other brain diseases later in life. TBI can impact cognitive health by damaging nerve cells and synapses (the specialized structures nerve cells use to send signals to one another and communicate). To better prevent TBI-related brain disease, scientists will need to clarify the biological mechanisms underlying how TBI damages brain function.
In initial research, Dr. Jaclyn Iannucci and colleagues have been studying an enzyme (cutting protein) called macrophage migration inhibitor factor (MIF). MIF normally helps promote macrophages and other immune system cells to eliminate harmful substances from the body. Individuals with Alzheimer’s or TBI, however, have elevated levels of MIF in their brains, which may lead to harmful brain inflammation and brain damage. The researchers found that in the brains of genetically engineered Alzheimer’s-like mice with TBI or elevated MIF, nerve cells important for learning and memory lost their ability to communicate through synapses. They also found that by reducing MIF activity in mice that recently underwent TBI, they could prevent TBI-related increases in the activity of “helper” cells called astrocytes (activity that can lead to brain inflammation). Taken together, these findings suggest MIF plays an important role in brain cell dysfunction following TBI – dysfunction that can lead to an increased risk for dementia.
Research Plan
Dr. Iannucci and colleagues will now confirm and expand on their earlier findings. After administering a form of TBI to male and female Alzheimer’s-like mice, they will assess how the TBI impacted (1) the animals’ brain cell and synaptic structure, (2) brain inflammation and (3) behavioral and cognitive function. As part of this experiment, the researchers will determine how TBI-related damage may impact male and female mice differently. Dr. Iannucci and team will then test whether preventing MIF activity after TBI can restore brain cell function in the mice.
Impact
Results from this study could improve our understanding of the links between TBI and brain disease. They could also lead to novel TBI therapies that target MIF – therapies that could restore brain health and lower post-TBI risk for Alzheimer’s.