Age- and sex-related changes make female flies vulnerable to delayed damage from head injuries

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Exposure of adult fruit flies to a very mild form of repeated head impacts at different ages causes minimal acute effects. Credit: (2024). DOI: 10.7554/eLife.97908.1

A research team from Emory University in Atlanta, Georgia, USA has found that even very mild, non-fatal head injuries at a young age can lead to neurodegenerative diseases as we age.

Using fruit flies as a model, the researchers found that chronic immunosuppression after mating could predispose female fruit flies to delayed brain damage due to head injuries early in life.

The study, published today as a graded preprint eLife, is described by the editors as foundational work that advances our understanding of how sex-dependent responses to traumatic brain injury occur. It provides what they call compelling results showing the immune and reproductive pathways that may contribute to these differences.

Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration later in life. However, identifying a causal relationship between exposure to mild head trauma in early life and the occurrence of neurodegeneration later in life is challenging, and it remains unclear how gender and age amplify outcomes.

“With their short lives, fruit flies allow scientists to monitor changes associated with brain injury throughout their lives,” said lead author Changtian Ye, a graduate student in the Emory Neuroscience Program, and member of senior author James Zheng’s laboratory. the Emory University School of Medicine. “We recently developed a fruit fly model of mild traumatic brain injury that allows us to induce mild head-on collisions and then monitor what happens in male and female flies from the time of injury to the onset of brain damage later in life.”

Using their model, Ye and colleagues monitored the impact of mild traumatic brain injury on the flies’ behavior. Although injury initially caused minimal acute deficits in the flies, it led to deeper brain-related behavioral disorders and degeneration later in life, and these conditions worsened with age. Furthermore, they were disproportionately high in women, which affected their climbing speed and ability, leaving them with more damaged brain tissue than their male counterparts.

The researchers also found that female flies that had mated had worse outcomes than unpaired (virgin) flies. They identified a protein called sex peptide – which is transferred to the female reproductive tract via sperm during mating – as a key player in making these flies more susceptible to the damaging effects of brain injury.

“Our analysis of the flies’ RNA data suggested that the chronic suppression of innate immune defense networks in paired females exposed to sex peptide makes them disproportionately vulnerable to neurodegeneration after mild head trauma,” Ye explains.

Together, the findings support the idea that head injuries can pose a major threat to brain health, even if mild, and that women may be disproportionately affected. The authors say additional studies are now needed to determine whether similar processes occur in other species.

“Our work establishes a causal link between early head trauma and neurodegeneration later in life, highlighting sex differences in the response to injury and the impact of age during and after injury,” concluded senior author James Zheng, principal investigator at the Zheng Lab, Emory University School. of medicine.

“It will be interesting to understand whether this relationship occurs in other organisms, and to dissect the genetic components and molecular players involved in the sex-different development of neurodegenerative disorders after mild head trauma.”

More information:
Changtian Ye et al., Sexual dimorphism in age-dependent neurodegeneration after mild head trauma in Drosophila: revealing the adverse consequences of female reproductive signaling, eLife (2024). DOI: 10.7554/eLife.97908.1

Magazine information:

Quote: Age- and sex-related changes make female flies vulnerable to delayed damage from head injury (2024, June 4) retrieved June 4, 2024 from .html

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