Distinct Aging-Vulnerable and -Resilient Trajectories of Specific Motor Circuit Functions in Oxidation- and Temperature-Stressed<i>Drosophila</i>

Iyengar, Atulya; Ruan, Hongyu; Wu, Chun Fang

doi:10.1523/eneuro.0443-21.2021

Cited by 3 publications

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References 127 publications

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“…Lifespans were performed as described in (Iyengar et al, 2022). Flies were collected in a 1-day age-range under CO 2 anesthesia and kept in standard vials.…”

Section: Methodsmentioning

confidence: 99%

Glial expression ofDrosophila UBE3Acauses spontaneous seizures modulated by 5-HT signaling

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Landaverde,

Lacoste

et al. 2024

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Misexpression of the E3 ubiquitin ligaseUBE3Ais thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, excess genomic copies ofUBE3Ais thought to contribute to the autism, muscle tone and spontaneous seizures characteristic of the disorder. In a Drosophila model of Dup 15q syndrome, it was recently shown glial-driven expression of theUBE3Aortholog dube3a led to a "bang-sensitive" phenotype, where mechanical shock triggers convulsions, suggesting glial dube3a expression contributes to hyperexcitability in flies. Here we directly compare the consequences of glial- and neuronal-drivendube3aexpression on motor coordination and neuronal excitability in Drosophila. We utilized IowaFLI tracker and developed a hidden Markov Model to classify seizure-related immobilization. Both glial and neuronal drivendube3aexpression led to clear motor phenotypes. However, only glial-driven dube3a expression displayed spontaneous immobilization events, that were exacerbated at high-temperature (38 °C). Using a tethered fly preparation we monitored flight muscle activity, we found glial-drivendube3aflies display spontaneous spike discharges which were bilaterally synchronized indicative of seizure activity. Neither control flies, nor neuronal-dube3a overexpressing flies display such firing patterns. Prior drug screen indicated bang-sensitivity in glial-driven dube3a expressing flies could be suppressed by certain 5-HT modulators. Consistent with this report, we found glial-drivendube3aflies fed the serotonin reuptake inhibitor vortioxetine and the 5HT2A antagonist ketanserin displayed reduced immobilization and spike bursting. Together these findings highlight the potential for glial pathophysiology to drive Dup15q syndrome-related seizure activity.

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“…Lifespans were performed as described in (Iyengar et al, 2022). Flies were collected in a 1-day age-range under CO 2 anesthesia and kept in standard vials.…”

Section: Methodsmentioning

confidence: 99%