Affiliations: 1) University of California, Davis; 2) University of Kansas
Keywords: a. neural degeneration; i. aggression
Traumatic brain injury (TBI) is a disruption of normal brain function that results from mild to severe impacts to the head, and can affect memory, as well as behaviors such as anxiety, aggression, and depression. In addition, TBI is the leading risk factor for late onset neurodegenerative diseases such as Alzheimer’s Disease. One major hallmark of TBI is the presence of hyperphosphorylated tau in the brain and cerebrospinal fluid. In a healthy brain, tau is a microtubule associated protein that controls microtubule based processes, but upon hyperphosphorylation, tau forms aggregates called neurofibrillary tangles (NFTs) that are thought to contribute to neurodegeneration. However, the series of events that cause tau hyperphosphorylation and NFT formation in response to injury, and how these contribute to neurodegeneration are not well established. We are utilizing a high impact method to subject flies expressing 2N4R human tau pan-neuronally to TBI in an effort to study the contribution of tau phosphorylation and oligomerization to neurodegeneration and behavioral decline. At 24 hours after inflicting TBI on 1 week old virgin males, we recorded flies to observe courtship and aggression. We found that pan-neuronal expression of tau caused an increase in inter-male aggression in flies subjected to TBI, both in terms of the amount of time engaged in aggressive acts and in the total number of aggressive acts. We have screened a variety of specific drivers for neuronal types known to be involved in mating and aggressive behaviors, and have identified dopaminergic and serotonergic circuits as contributors to increased aggression. In addition to our behavioral studies, we are performing immunohistochemistry on fly brains from 24 hours, 1 week, or 3 weeks post-injury to determine if there are any differences in tau localization and/or neurodegeneration. The neurodegeneration associated with TBI and tau expression in Drosophila can be indicated via the presence of vacuoles. We aim to determine if coupling TBI and tau expression affects tau localization or exacerbates the occurrence of neurodegeneration seen with TBI or tau expression alone. In addition, we are analyzing the phosphorylation and aggregation of tau isolated from fly brains using biochemical techniques. Ultimately, we hope to elucidate how different molecular states of tau contribute to neurodegeneration and lead to alterations in brain function and behaviors.