Drosophila Stat92E Signaling Following Pre-exposure to Ethanol

Abstract

Repeated exposure to alcohol alters neuromolecular signaling that influences acute and long-lasting behaviors underlying Alcohol Use Disorder (AUD). Recent animal model research has implicated changes in the conserved JAK/STAT pathway, a signaling pathway classically associated with development and the innate immune system. How ethanol exposure impacts STAT signaling within neural cells is currently unclear. Here, we investigated the role of Drosophila Stat92E in ethanol-induced locomotion, signaling activity, and downstream transcriptional responses. Findings suggest that expressing Stat92E-RNAi causes enhanced ethanol-induced hyperactivity in flies previously exposed to ethanol. Furthermore, alternative splicing of Stat92E itself was detected after repeated ethanol exposure, although no changes were found in downstream transcriptional activity. This work adds to our growing understanding of altered neuromolecular signaling following ethanol exposure and suggests that STAT signaling may be a relevant target to consider for AUD treatment.

TBI and Tau Loss of Function Both Affect Naïve Ethanol Sensitivity in Drosophila

“…These two pathways are also activated by axonal injury and interact to regulate axon regeneration [ 78 , 79 ]. Interestingly, the knockdown of STAT92E, the only STAT ortholog in Drosophila , led to significantly higher ethanol-induced locomotor behavior in flies previously exposed to ethanol [ 80 ]. It is not currently known if this increased sensitivity to the activating properties of ethanol translates to an increased sensitivity to the sedating effects of this drug [ 80 ].…”

“…Interestingly, the knockdown of STAT92E, the only STAT ortholog in Drosophila , led to significantly higher ethanol-induced locomotor behavior in flies previously exposed to ethanol [ 80 ]. It is not currently known if this increased sensitivity to the activating properties of ethanol translates to an increased sensitivity to the sedating effects of this drug [ 80 ]. It remains possible that the loss-of-STAT92E activity would impair post-TBI axon recovery, leading to an increased sensitivity to ethanol sedation.…”

TBI and Tau Loss-of-Function Both Affect Naïve Ethanol Sensitivity in Drosophila

“…These two pathways are also activated by axonal injury and interact to regulate axon regeneration [78,79]. Interestingly, the knockdown of STAT92E, the only STAT ortholog in Drosophila, led to significantly higher ethanolinduced locomotor behavior in flies previously exposed to ethanol [80]. It is not currently known if this increased sensitivity to the activating properties of ethanol translates to an increased sensitivity to the sedating effects of this drug [80].…”

“…Interestingly, the knockdown of STAT92E, the only STAT ortholog in Drosophila, led to significantly higher ethanolinduced locomotor behavior in flies previously exposed to ethanol [80]. It is not currently known if this increased sensitivity to the activating properties of ethanol translates to an increased sensitivity to the sedating effects of this drug [80]. It remains possible that the loss-of-STAT92E activity would impair post-TBI axon recovery, leading to an increased sensitivity to ethanol sedation.…”

Drosophilalearning and memory centers and the actions of drugs of abuse

“…Other targets of the Notch/Su(H) pathway showed shifts in gene isoform expression with ethanol spaced training, including the Stat92E gene that encodes a component of the JAK/STAT signaling pathway and that functions in the mushroom bodies for alcohol-associative preference (Petruccelli et al 2018(Petruccelli et al , 2020Wilson et al 2023). The Stat92E isoform switching induced by ethanol spaced training was still detectable at 24 hours, when ethanol reward memories are typically tested.…”