Early social isolation accelerates TDP-43 neurodegeneration and shortens lifespan in fruit flies

In fruit flies (Drosophila), early-life social isolation accelerates TDP-43-dependent neurodegeneration, according to a new preprint. Researchers compared young adult flies housed alone to those kept in socially enriched groups before inducing pathological levels of TDP-43. Early-life isolation primed the flies for more rapid neurodegeneration and shortened their lifespan. Isolated flies showed faster activation of mdg4, an endogenous retrovirus that functionally mediates TDP-43 effects. Isolation stress also spurred more aggressive propagation of TDP-43 protein pathology from surface glial cells to nearby neurons. Providing isolated flies with visual, olfactory, and tactile cues from conspecifics behind a divider failed to alleviate these neurodegenerative effects.