View Program - 63rd Annual Drosophila Research Conference

Traumatic brain injury (TBI) shares molecular and cellular hallmarks with neurodegenerative diseases (NDs), and is a major risk factor for developing neurodegeneration later in life. While our understanding of genes and pathways that underlie neurotoxicity in specific NDs has advanced, we still lack a complete understanding of molecular and physiological changes that drive neurodegeneration as an individual ages following a TBI. In recent years, many different studies have introduced Drosophila as a model organism for studying closed-head TBI, though they have primarily focused on acute or short-term outcomes of the TBI. In our research, we delivered a TBI to flies early in adult life, and then measured molecular and physiological phenotypes at short-, mid-, and long-term timepoints following the injury. We aim to identify the timing of changes that may contribute to progressive neurodegeneration, following a TBI. We confirmed prior work demonstrating a TBI-induced decline in lifespan, and uncovered evidence of a progressive decline in locomotor function, robust acute and modest chronic neuroinflammation, and a late-onset increase in protein aggregation. We also found evidence of metabolic dysfunction, in the form of starvation sensitivity and decreased lipids, that persisted beyond the immediate injury response, but resolved long-term. An intervention of dietary restriction (DR), or a low-protein diet, partially ameliorated some TBI-induced phenotypes, such as lifespan and locomotor function, though it did not alter the starvation sensitivity of injured flies. In the future, identifying molecular pathways altered in the short- or mid-term following TBI could suggest causality and point towards potential therapeutic targets.

Dietary restriction ameliorates TBI-induced phenotypes in Drosophila melanogaster.

**Dietary restriction ameliorates TBI-induced phenotypes in Drosophila melanogaster.**