Biology subjects

Agosto, J. L.

Publications and source records attributed to Agosto, J. L..

3 recordsLinked to original sources

bioRxiv2024

Alcohol-induced sleep dysregulation in Drosophila is dependent on the neuropeptide PDF

Alcohol exposure is known to trigger homeostatic adaptations in the brain that lead to the development of tolerance and dependence. These adaptations are also believed to be the root of a series of disturbances in sleep patterns that often manifest during the development of alcoholism and can have significant clinical and economic consequences. Unfortunately, the neuronal and genetic pathways that control the effects of alcohol on sleep are currently unknown, thus limiting our efforts to find effective treatment. In this study, we conduct a mechanistic exploration of the relationships between alcohol and sleep alterations using a Drosophila model system. We show that the genetic manipulation of the ventral lateral neurons (LNv) --a set of neurons known to control sleep in Drosophila-- disrupts alcohol sensitivity and tolerance. Moreover, we show that alcohol exposure induces a series of alterations in sleep patterns that last for several days. Our results demonstrate that a single alcohol exposure promotes daytime sleep, alters the structure of sleep during the night, and reduces morning anticipatory behavior. In addition, we show that some of these alterations partially depend on the activity of the neuropeptide PDF, a key element in regulating sleep architecture. We propose that alcohol-induced sleep disruption stems from alterations in the activity of the PDF-releasing LNv neurons and that these alterations are similar to those that produce alcohol tolerance.

neuroscience↗

bioRxiv2023

Effects of lithium on locomotor activity and circadian rhythm of honey bees

The miticide effect of lithium on the honey bee (Apis mellifera) parasite Varroa has been discovered. Varroa mite is considered the principal threat to bee health and, as a result, to pollination and food security. In this study, we investigated the behavioral effects of lithium on honey bees, specifically locomotor activity (LMA) level and circadian patterns of LMA, such as rhythmicity, and periodicity. Any effects of lithium on activity may be important for bee health since timing and daylight are critical for bee foraging and bees use of the sun compass for navigation and communication. Both acute and chronic lithium treatments affected the LMA of honey bees. The effect varies depending on light and dark conditions. Chronic treatment with lithium disrupted the rhythmicity and altered the period of the circadian rhythm. While the circadian period was not affected by the light condition in the control group, lithium treatment lengthened the period in constant light condition. Lithium decreased total LMA in a constant light condition where typically activity is increased and not under the dark condition, both in acute and chronic treatments. However, mortality in the high-dose lithium treatment group is higher in the dark environment in the acute experiment. Lithium is also the first-line therapy for bipolar disorder. This disorder causes excessively elevated activity called mania and circadian rhythm abnormalities. The effects of lithium on reducing light-induced activity and the circadian rhythm of bees are reminiscent of its stabilizing effect on activity and circadian rhythms in bipolar disorder treatment.

neuroscience↗

bioRxiv2019

pumilio regulates sleep homeostasis in response to chronic sleep deprivation in Drosophila melanogaster

Recent studies have identified the Drosophila brain circuits involved in the sleep/wake switch and have pointed to the modulation of neuronal excitability as one of the underlying mechanisms triggering sleep need. In this study we aimed to explore the link between the homeostatic regulation of neuronal excitability and sleep behavior in the circadian circuit. For this purpose, we selected the neuronal homeostasis protein Pumilio (Pum), whose main function is to repress protein translation and has been linked to modulation of neuronal excitability during chronic patterns of altered neuronal activity. Here we explore the effects of Pum on sleep homeostasis in Drosophila melanogaster, which shares most of the major features of mammalian sleep homeostasis. Our evidence indicates that Pum is necessary for sleep rebound and that its effect is more pronounced during chronic sleep deprivation (84 hours) than acute deprivation (12 hours). Knockdown of pum, results in a reduction of sleep rebound during acute sleep deprivation and the complete abolishment of sleep rebound during chronic sleep deprivation. These behavioral changes were associated with accompanying changes in the expression of genes involved in the regulation of neuronal excitability. Interestingly, pum knockdown also increased baseline daytime sleep, suggesting that Pum differentially regulates rebound and normal sleep. Based on these findings, we propose that Pum is a critical regulator of sleep homeostasis through neural adaptations triggered during sleep deprivation and induces rebound sleep by altering neuronal excitability.

neuroscience↗