The Role of Glial Peroxisome in Neuron-Glia Communication in Drosophila

Peroxisome function in glial cells has been shown to impact neuronal functions. In the present study, we aim to elucidate the mechanism behind peroxisome-mediated glia-neuron communication using Drosophila as a model organism. I used the UAS-gal4 system to drive RNAi knockdown or overexpression in either glia tissue or motor neurons. The morphology of the axons directly preceding the abdominal neuromuscular junction (NMJ) was visualized using confocal microscopy and the axonal area and volume was quantified via ImageJ. Glial-specific knockdown of peroxisome import protein, Pex5, using pan-glial driver repo-gal4 resulted in increased axonal area and volume as compared to the control. Consistent with our previous work showing defective peroxisomes upregulate inflammatory cytokine upd3 and JAK-STAT signaling, overexpression of upd3 in glia increases axonal volume and area. We further show that neuronal-specific activation of the JAK-STAT pathway through hop overexpression results in an increase in axon size. Taken together, our findings suggest that impairment of peroxisomes in the glia impacts axonal morphology and potentially function via inflammatory response, specifically the JAK-STAT pathway

The Role of Glial Peroxisome in Neuron-Glia Communication in Drosophila

Peroxisome function in glial cells has been shown to impact neuronal functions. In the present study, we aim to elucidate the mechanism behind peroxisome-mediated glia-neuron communication using Drosophila as a model organism. I used the UAS-gal4 system to drive RNAi knockdown or overexpression in either glia tissue or motor neurons. The morphology of the axons directly preceding the abdominal neuromuscular junction (NMJ) was visualized using confocal microscopy and the axonal area and volume was quantified via ImageJ. Glial-specific knockdown of peroxisome import protein, Pex5, using pan-glial driver repo-gal4 resulted in increased axonal area and volume as compared to the control. Consistent with our previous work showing defective peroxisomes upregulate inflammatory cytokine upd3 and JAK-STAT signaling, overexpression of upd3 in glia increases axonal volume and area. We further show that neuronal-specific activation of the JAK-STAT pathway through hop overexpression results in an increase in axon size. Taken together, our findings suggest that impairment of peroxisomes in the glia impacts axonal morphology and potentially function via inflammatory response, specifically the JAK-STAT pathway

The Role of Glial Peroxisome in Neuron-Glia Communication in Drosophila

Peroxisome function in glial cells has been shown to impact neuronal functions. In the present study, we aim to elucidate the mechanism behind peroxisome-mediated glia-neuron communication using Drosophila as a model organism. I used the UAS-gal4 system to drive RNAi knockdown or overexpression in either glia tissue or motor neurons. The morphology of the axons directly preceding the abdominal neuromuscular junction (NMJ) was visualized using confocal microscopy and the axonal area and volume was quantified via ImageJ. Glial-specific knockdown of peroxisome import protein, Pex5, using pan-glial driver repo-gal4 resulted in increased axonal area and volume as compared to the control. Consistent with our previous work showing defective peroxisomes upregulate inflammatory cytokine upd3 and JAK-STAT signaling, overexpression of upd3 in glia increases axonal volume and area. We further show that neuronal-specific activation of the JAK-STAT pathway through hop overexpression results in an increase in axon size. Taken together, our findings suggest that impairment of peroxisomes in the glia impacts axonal morphology and potentially function via inflammatory response, specifically the JAK-STAT pathway

The Role of Glial Peroxisome in Neuron-Glia Communication in Drosophila

Peroxisome function in glial cells has been shown to impact neuronal functions. In the present study, we aim to elucidate the mechanism behind peroxisome-mediated glia-neuron communication using Drosophila as a model organism. I used the UAS-gal4 system to drive RNAi knockdown or overexpression in either glia tissue or motor neurons. The morphology of the axons directly preceding the abdominal neuromuscular junction (NMJ) was visualized using confocal microscopy and the axonal area and volume was quantified via ImageJ. Glial-specific knockdown of peroxisome import protein, Pex5, using pan-glial driver repo-gal4 resulted in increased axonal area and volume as compared to the control. Consistent with our previous work showing defective peroxisomes upregulate inflammatory cytokine upd3 and JAK-STAT signaling, overexpression of upd3 in glia increases axonal volume and area. We further show that neuronal-specific activation of the JAK-STAT pathway through hop overexpression results in an increase in axon size. Taken together, our findings suggest that impairment of peroxisomes in the glia impacts axonal morphology and potentially function via inflammatory response, specifically the JAK-STAT pathway

FOXO Regulates Neuromuscular Junction Homeostasis During Drosophila Aging

The transcription factor foxo is a known regulator of lifespan extension and tissue homeostasis. It has been linked to the maintenance of neuronal processes across many species and has been shown to promote youthful characteristics by regulating cytoskeletal flexibility and synaptic plasticity at the neuromuscular junction (NMJ). However, the role of foxo in aging neuromuscular junction function has yet to be determined. We profiled adult Drosophila foxo- null mutant abdominal ventral longitudinal muscles and found that young mutants exhibited morphological profiles similar to those of aged wild-type flies, such as larger bouton areas and shorter terminal branches. We also observed changes to the axonal cytoskeleton and an accumulation of late endosomes in foxo null mutants and motor neuron-specific foxo knockdown flies, similar to those of aged wild-types. Motor neuron-specific overexpression of foxo can delay age-dependent changes to NMJ morphology, suggesting foxo is responsible for maintaining NMJ integrity during aging. Through genetic screening, we identify several downstream factors mediated through foxo-regulated NMJ homeostasis, including genes involved in the MAPK pathway. Interestingly, the phosphorylation of p38 was increased in the motor neuron-specific foxo knockdown flies, suggesting foxo acts as a suppressor of p38/MAPK activation. Our work reveals that foxo is a key regulator for NMJ homeostasis, and it may maintain NMJ integrity by repressing MAPK signaling.This article is published as Birnbaum A, Sodders M, Bouska M, Chang K, Kang P, McNeill E and Bai H (2021) FOXO Regulates Neuromuscular Junction Homeostasis During Drosophila Aging. Front. Aging Neurosci. 12:567861. doi: 10.3389/fnagi.2020.567861. Posted with permission. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

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

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