bioRxiv Science⌕ Search

Biology subjects

Gugala, F.

Publications and source records attributed to Gugala, F..

2 recordsLinked to original sources

Environmental modulation of social isolation-induced sleep loss in Drosophila

Chronic social isolation induces persistent behavioral and physiological changes across species. In humans, prolonged social isolation is associated with insomnia and increased risks of cognitive decline, cardiovascular disease, compromised immunity, and premature mortality. Yet whether these consequences are modified by the environment in which social isolation is experienced remains unclear. In particular, can access to social sensory information from conspecifics alleviate the effects of isolation and can various ambient environmental settings modify them? A related question arises during behavioral measurement because behavioral assays themselves impose a new environmental context. Whether these assays simply capture the enduring effects of prior social experience or further modify those effects remains unknown. Using social isolation-induced sleep loss in Drosophila as a model, we systematically examined how the social, spatial, and photoperiodic environments during isolation and behavioral monitoring influence the isolation phenotype. Providing isolated flies with visual, olfactory, or tactile social cues from conspecifics living behind a divider, either individually or in combination, was insufficient to alleviate sleep loss. Spatial confinement exacerbated isolation-induced sleep loss, while winter-like photoperiod in spatially confined Drosophila Activity Monitor assays revealed the clearest progressive decline in sleep during sleep monitoring. Together, these findings demonstrate that social isolation-induced sleep loss is both enduring and dynamic: it persists despite exposure to social cues yet remains sensitive to the environmental context in which isolation is experienced and behavior is measured. More broadly, our study establishes a tractable framework for investigating the environmental modulation of chronic social isolation.

neuroscience↗

Early life social isolation primes flies for more rapid TDP-43 dependent neurodegeneration later in life.

A key pathophysiological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is loss of nuclear localization and abnormal cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43). Upstream factors that trigger the onset and progression of such neurodegenerative diseases are largely unknown. Aging and environmental factors contribute as potential risk factors. But epidemiological evidence suggests psychological stressors such as social isolation and loneliness are also associated with increased risks of neurodegenerative disease [1-8]. We examined the impacts of social isolation on TDP-43 related neurodegeneration. To investigate the potential for causative impact on neurodegeneration, we compared the effects of social isolation versus social enrichment in Drosophila. We utilized an established social isolation paradigm in which flies were either housed alone or in groups as young adults. We found that early-life social isolation acts as a primer to exacerbate the rate of neurodegeneration in response to subsequent induction of pathological levels of TDP-43. Social isolation stress drives more rapid activation of mdg4, an endogenous retrovirus that functionally mediates TDP-43 effects and more aggressive propagation of TDP-43 protein pathology from surface glial cells to nearby neurons. Shortened life span also ensues. We demonstrate that providing isolated flies with visual, olfactory and tactile social cues from conspecifics living behind a divider was insufficient to alleviate these effects of social isolation on neurodegeneration. Our findings have implications for the association between psychological stressors such as loneliness and risk of neurodegenerative diseases in humans and provide a platform to investigate mechanistic underpinnings in animal models.

neuroscience↗