Milk-whey diet substantially suppresses seizure-like phenotypes ofparaShu, aDrosophilavoltage-gated sodium channel mutant

Kasuya, Junko; Iyengar, Atulya; Chen, Hung-Lin; Lansdon, Patrick; Wu, Chun‐Fang; Kitamoto, Toshihiro

doi:10.1080/01677063.2019.1597082

Cited by 26 publications

(20 citation statements)

References 67 publications

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“…Analysis of decapitated flies and Ring-X gynandromorph mosaics has further indicated both ID and DD pattern generators reside in the thorax, although globally synchronized episodes of electric activities and quiescence concurrent with ID, paralysis and DD also emerge in different parts of the CNS (Lee and Wu, 2002). However, the ID and DD are likely derived from separable network origins, as they are independently vulnerable to different ion channel mutations (Lee and Wu, 2006;Kasuya et al, 2019).…”

Section: Electroconvulsive Seizurementioning

confidence: 99%

Distinct aging-vulnerable trajectories of motor circuit functions in oxidation- and temperature-stressedDrosophila

Iyengar

Ruan

2020

Preprint

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We examined several sensory-motor processing circuits in Drosophila across the lifespan and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties. We observed relatively little deterioration toward the end of lifespan in the giant-fiber (GF) and downstream circuit elements responsible for the jump-and-flight escape reflex. In contrast, we found substantial age-dependent modifications in the performance of GF inputs and other circuits driving flight motoneuron activities. Importantly, in high temperature (HT)-reared flies (29 °C), the characteristic age-dependent progression of these properties was largely maintained, albeit over a compressed time scale, lending support for the common practice of expediting Drosophila aging studies by HT rearing. We discovered shortened lifespans in Cu2+/Zn2+ Superoxide Dismutase 1 (Sod) mutant flies were accompanied by alterations distinct from HT-reared flies, highlighting differential effects of oxidative vs temperature stressors. This work also establishes several age-vulnerable parameters that may serve as quantitative neurophysiological landmarks for aging in Drosophila.

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Section: Electroconvulsive Seizurementioning

confidence: 99%

Distinct aging-vulnerable trajectories of motor circuit functions in oxidation- and temperature-stressedDrosophila

Iyengar

Ruan

2020

Preprint

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“…Sun et al (2012) and Schutte et al (2014) created Drosophila para knock-in alleles, gain-of-function para GEFS+ and loss-of-function para DS , by introducing a disease-causing human GEFS+ or DS mutation at the corresponding position of the fly Na v -channel gene. At 40 o C, para GEFS+ homozygous females and hemizygous males exhibit a temperature-induced seizure-like behavior that is similar to, but milder than, that observed in para Shu flies (SUN et al 2012;KAAS et al 2016;KASUYA et al 2019). para DS flies lose their posture shortly after being transferred to 37 o C (SCHUTTE et al 2014).…”

Section: Gsts1 M26 Suppresses the Phenotypes Of Other Para Gain-of-fumentioning

confidence: 97%

“…Flies were reared at 25C, 65% humidity in a 12 hr light/dark cycle on a cornmeal/glucose/yeast/agar medium supplemented with the mold inhibitor methyl 4hydroxybenzoate (0.05 %). The exact composition of the fly food used in this study was described in Kasuya et al (2019). The Canton-S (CS) strain was used as the wild-type control.…”

Section: Fly Stocks and Culture Conditionsmentioning

confidence: 99%

“…Adult para Shu mutants exhibit various dominant phenotypes in addition to shuddering, such as defective climbing behavior, increased susceptibility to electroconvulsive and heatinduced seizures, and short lifespan. They also have an abnormal down-turned wing posture and an indented thorax, both of which are thought to be caused by neuronal hyperexcitability (WILLIAMSON 1982;KAAS et al 2016;KASUYA et al 2019). In the current study, we carried out a forward genetic screen for dominant modifiers of para Shu and found that the phenotypes are significantly suppressed by loss-of-function mutations in the glutathione S-transferase S1 (GstS1) gene.…”

Section: Introductionmentioning

confidence: 99%

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Reduced Function of the Glutathione S-Transferase S1 Suppresses Behavioral Hyperexcitability inDrosophilaExpressing Mutant Voltage-Gated Sodium Channels

Chen¹,

Kasuya

Lansdon³

et al. 2020

G3 Genes|Genomes|Genetics

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Voltage-gated sodium (Nav) channels play a central role in the generation and propagation of action potentials in excitable cells such as neurons and muscles. To determine how the phenotypes of Nav-channel mutants are affected by other genes, we performed a forward genetic screen for dominant modifiers of the seizure-prone, gain-of-function Drosophila melanogaster Nav-channel mutant, paraShu. Our analyses using chromosome deficiencies, gene-specific RNA interference, and single-gene mutants revealed that a null allele of glutathione S-transferase S1 (GstS1) dominantly suppresses paraShu phenotypes. Reduced GstS1 function also suppressed phenotypes of other seizure-prone Nav-channel mutants, paraGEFS+ and parabss. Notably, paraShu mutants expressed 50% less GstS1 than wild-type flies, further supporting the notion that paraShu and GstS1 interact functionally. Introduction of a loss-of-function GstS1 mutation into a paraShu background led to up- and down-regulation of various genes, with those encoding cytochrome P450 (CYP) enzymes most significantly over-represented in this group. Because GstS1 is a fly ortholog of mammalian hematopoietic prostaglandin D synthase, and in mammals CYPs are involved in the oxygenation of polyunsaturated fatty acids including prostaglandins, our results raise the intriguing possibility that bioactive lipids play a role in GstS1-mediated suppression of paraShu phenotypes.

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“…Flies were reared on Frankel & Brosseau (1968) cornmeal-based media (see Kasuya et al, 2019) at room temperature (23 °C). To make PQ-laced media, measured amounts of paraquat (Sigma #856177) and Blue #1 dye (to indicate mixing, flavorsandcolor.com, Diamond Bar, CA) were added to melted fly media to achieve final concentrations of 5 or 10 mM PQ and 25 μ g/ml dye.…”

Section: Fly Stocks and Drug Feedingmentioning

confidence: 99%

Differential effects on neuromuscular physiology betweenSodloss-of-function mutation and paraquat-induced oxidative stress inDrosophila

Ueda

Iyengar

2021

Preprint

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Oxidative stress is thought to be a major contributor to aging processes. Here, we report differential effects on neurotransmission caused by loss-of-function mutations of Superoxide dismutase (Sod) and by paraquat (PQ) feeding in Drosophila. We demonstrated alterations in Sod mutants; the larval neuromuscular junction displayed supernumerary discharges and the adult giant-fiber escape pathway showed increased latency and poor response to repetitive high-frequency stimulation. Even though the concentrations used led to motor coordination defects and lethality, PQ feeding failed to reproduce such performance deficits in these larval and adult preparations, indicating mechanistic distinctions between genetic and pharmacological manipulation of oxidative stress.

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Milk-whey diet substantially suppresses seizure-like phenotypes ofpara^Shu, aDrosophilavoltage-gated sodium channel mutant

Cited by 26 publications

References 67 publications

Distinct aging-vulnerable trajectories of motor circuit functions in oxidation- and temperature-stressedDrosophila

Distinct aging-vulnerable trajectories of motor circuit functions in oxidation- and temperature-stressedDrosophila

Reduced Function of the Glutathione S-Transferase S1 Suppresses Behavioral Hyperexcitability inDrosophilaExpressing Mutant Voltage-Gated Sodium Channels

Differential effects on neuromuscular physiology betweenSodloss-of-function mutation and paraquat-induced oxidative stress inDrosophila

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