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bioRxiv · 10.1101/2024.03.06.583747

Sexual Dimorphism in Age-Dependent Neurodegeneration After Mild Head Trauma in Drosophila: Unveiling the Adverse Impact of Female Reproduction

Ye, C.·Ho, R.·Moberg, K.·Zheng, J. Q.
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Abstract

Environmental insults, including mild head trauma, significantly increase the risk of neurodegeneration. However, it remains challenging to establish a causative connection between early-life exposure to mild head trauma and late-life emergence of neurodegenerative deficits, nor do we know how sex and age compound the outcome. Using a Drosophila model, we demonstrate that exposure to mild head trauma causes neurodegenerative conditions that emerge late in life and disproportionately affect females. Increasing age-at-injury further exacerbates this effect in a sexually dimorphic manner. We further identify Sex Peptide (SP) signaling as a key factor in female susceptibility to post-injury brain deficits. RNA sequencing highlights a reduction in innate immune defense transcripts specifically in mated females during late life. Our findings establish a causal relationship between early head trauma and late-life neurodegeneration, emphasizing sex differences in injury response and the impact of age-at-injury. Finally, our findings reveal that reproductive signaling adversely impacts female response to mild head insults and elevates vulnerability to late-life neurodegeneration.

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Ye, C., Ho, R., Moberg, K., Zheng, J. Q.. 2024-03-10. Sexual Dimorphism in Age-Dependent Neurodegeneration After Mild Head Trauma in Drosophila: Unveiling the Adverse Impact of Female Reproduction. https://doi.org/10.1101/2024.03.06.583747

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