Impact of Traumatic Brain Injury on Astrocytic Tau Pathology in Drosophila melanogaster
Date
2023-06-28
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Abstract
The protein tau is involved in the pathology of neurodegeneration through development
into aggregates by abnormal hyperphosphorylation events. Tau is mostly expressed in neurons,
but tau pathology in glial cells is seen as a hallmark of many neurodegenerative diseases.
Traumatic brain injury (TBI) is known to enhance this formation of tau aggregates and relative
toxicity from its expression in neurons and glia. While there are emerging discoveries
surrounding the relationship between tau and TBI, the time point/exposure level in which TBI
can incite robust aggregation and toxicity has not been explored in a cell-type specific disease
model. In this study, we used Drosophila melanogaster as a model of tau overexpression in
astrocytes, a major glial cell of the brain. We then exposed flies to various amounts of TBI at
various time points within their lifespan. We found that there was no difference in the presence
of tau aggregates at day 10, but there was a significantly higher mortality index at the same time
point in flies that were hit on four of the 10 days compared to flies hit on day 9 and flies that
were not hit at all. We found that flies hit on day 9 had significantly higher tau pathology at day
30 than flies hit later in life. Additionally, we saw that the females hit day 9 had significantly
higher tau pathology at day 30 compared to males with the same TBI exposure. We also saw a
decreased lifespan up to day 60 in flies hit multiple times compared to hit once or not at all.
These data suggests that toxicity is not linked to aggregate presence, and the tau toxicity
associated with the increase in mortality for flies who experienced multiple hits should be
explored.
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Keywords
Traumatic Brain Injury, Tau, Neurodegeneration, Astrocytes, Drosophila melanogaster