Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia

Doshi, Shachee; Price, Emma L.; Landis, Justin T.; Barot, Urva; Sabatella, Mariangela; Lans, Hannes; Kalb, Robert G.

doi:10.1016/j.freeradbiomed.2018.12.006

Cited by 6 publications

(16 citation statements)

References 53 publications

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“…Since the preconditioning phenomena has been described throughout the animal kingdom, insight into this physiological response in a genetically tractable organism may have broad application. [39][40][41] One salient feature of our investigations here and in prior publications (Flibotte et al, 2014 andDoshi et al,2019) is variability of survival after a 48-hour anoxic insult.…”

Section: Discussionmentioning

confidence: 65%

“…However, we think that is unlikely because previous work showed no difference in survival to anoxic stress between early versus late stage animals. 18 We therefore consider two, not mutually exclusive, possibilities to explain these observations. First, normal physiological activity of cholinergic and GABAergic neurons and muscle might secrete an “anoxia sensitivity factor” which heightens organismal vulnerability to anoxia.…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis was derived from the observations that: 1) inhibition of neuropeptide processing ( e.g ., C. elegans with egl-3 or egl-21 mutation) and secretion ( e.g ., C. elegans with unc-31 mutation) protected against anoxia, 2) nervous systemspecific rescue of egl-3 expression in egl-3 mutant animals restored sensitivity to anoxia, and 3) we identified one neuropeptide nlp-40 and its receptor aex-2 that are likely to be involved in this process. 18 These observations highlight the cell non-autonomous determinants of C. elegans survival upon anoxia insult.…”

Section: Introductionmentioning

confidence: 85%

“…Protocol and details described by Theresa Stiernagle in Wormbook chapter entitled Maintenance of C. elegans and used in previous studies to synchronize C. elegans for hypoxia assays in Flibotte et al ., 2014 and Doshi et al ., 2019. 13,18,24…”

Section: Methodsmentioning

confidence: 99%

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Preconditioning ofCaenorhabditis elegansto Anoxic Insult by Inactivation of Cholinergic, GABAergic, and Muscle Activity

Bennett

McClanahan

Fang-Yen

et al. 2020

Preprint

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For most metazoans, oxygen deprivation leads to cell dysfunction and if severe, death. Sublethal stress prior to a hypoxic or anoxic insult (“pre-conditioning”) can protect cells from subsequent oxygen deprivation. The molecular mechanisms by which sublethal stress can buffer against a subsequent toxic insult and the role of the nervous system in the response are not well understood. We studied the role of neuronal activity pre-conditioning to oxygen deprivation in C. elegans. Animals expressing the histamine gated chloride channels (HisCl1) in select cell populations were used to temporally and spatially inactivate the nervous system or tissue prior to an anoxic insult. We find that inactivation of the nervous system for 3 hours prior to the insult confers resistance to a 48-hour anoxic insult in 4th-stage larval animals. Experiments show that this resistance can be attributed to loss of activity in cholinergic and GABAergic neurons as well as in body wall muscles. These observations indicate that the nervous system activity can mediate the organism’s response to anoxia.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Preconditioning ofCaenorhabditis elegansto Anoxic Insult by Inactivation of Cholinergic, GABAergic, and Muscle Activity

Bennett

McClanahan

Fang-Yen

et al. 2020

Preprint

Self Cite

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“…AEX-2 serves as the NLP-40 receptor to regulate rhythmic behavior or anoxic survival (Wang et al, 2013; Doshi et al, 2019). To test whether aex-2 regulates AIY presynaptic assembly, we examined the fluorescent intensity of the presynaptic marker in aex-2(sa3) mutants and found a dramatic reduction in AIY GFP::RAB-3 intensity (Fig.…”

Section: Resultsmentioning

confidence: 99%

Gut regulates brain synaptic assembly through neuroendocrine signaling pathway

Shi

Shao

2021

Preprint

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The gut-brain axis plays an essential role in regulating neural development in response to external environmental stimuli, such as microbes or nutrient availability. Defects in gut-brain communication usually lead to various neurological disorders. However, it remains unknown whether gut plays any intrinsic role in regulating neuronal development. Through a genetic screen in C. elegans, we uncovered that an intrinsic Wnt-endocrine pathway in gut regulates synaptic development and neuronal activity in brain. Specifically, the gut expressed neuropeptide NLP-40 upregulated by a canonical Wnt signaling, which then facilitates presynaptic assembly through regulating GPCR AEX-2 mediated neuronal spontaneous activity. Therefore, this study not only uncovers a novel synaptic development mechanism, but also reveals a novel gut-brain interaction.

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Effect of the mitochondrial unfolded protein response on hypoxic death and mitochondrial protein aggregation

et al. 2021

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Mitochondria are the main oxygen consumers in cells and as such are the primary organelle affected by hypoxia. All hypoxia pathology presumably derives from the initial mitochondrial dysfunction. An early event in hypoxic pathology in C. elegans is disruption of mitochondrial proteostasis with induction of the mitochondrial unfolded protein response (UPRmt) and mitochondrial protein aggregation. Here in C. elegans, we screen through RNAis and mutants that confer either strong resistance to hypoxic cell death or strong induction of the UPRmt to determine the relationship between hypoxic cell death, UPRmt activation, and hypoxia-induced mitochondrial protein aggregation (HIMPA). We find that resistance to hypoxic cell death invariantly mitigated HIMPA. We also find that UPRmt activation invariantly mitigated HIMPA. However, UPRmt activation was neither necessary nor sufficient for resistance to hypoxic death and vice versa. We conclude that UPRmt is not necessarily hypoxia protective against cell death but does protect from mitochondrial protein aggregation, one of the early hypoxic pathologies in C. elegans.

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Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia

Cited by 6 publications

References 53 publications

Preconditioning ofCaenorhabditis elegansto Anoxic Insult by Inactivation of Cholinergic, GABAergic, and Muscle Activity

Preconditioning ofCaenorhabditis elegansto Anoxic Insult by Inactivation of Cholinergic, GABAergic, and Muscle Activity

Gut regulates brain synaptic assembly through neuroendocrine signaling pathway

Effect of the mitochondrial unfolded protein response on hypoxic death and mitochondrial protein aggregation

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