Biology subjects

Bennett, H. L.

Publications and source records attributed to Bennett, H. L..

4 recordsLinked to original sources

bioRxiv2026

Neuropeptide NLP-40 and Cognate G- Protein Coupled Receptor AEX-2 Regulate Behavioral Responses During Anoxia in Caenorhabditis elegans

Background: Insufficient oxygen (hypoxia) or complete lack of oxygen (anoxia) causes cellular dysfunction and death in terrestrial animals. As a result, animals have developed homeostatic strategies, including changes in movement strategies to escape and survive stressful environments. Caenorhabditis elegans respond to changes in oxygen by increasing the frequency of reversals (backward movement) and increasing locomotor speed; these behaviors enable them to escape unfavorable environments and move to more suitable ones. The molecular and neural mechanisms underlying behavioral responses to low-oxygen environments are incomplete. Neuropeptides regulate C. elegans behaviors by modifying neural circuit function in response to hypoxia. Loss of function in C. elegans neuropeptide nlp-40 and its receptor aex-2 increased survival to anoxia [1]. However, the cells in which NLP-40 and AEX-2 function for anoxia, as well as the mechanisms underlying responses to anoxia, remain elusive. We hypothesized that NLP-40 and AEX-2 regulate anoxia by altering escape behaviors. Results: We found that neuropeptide NLP-40 functions in cholinergic neurons and AEX-2 functions in cholinergic or GLR-1 interneurons or motor neurons to regulate susceptibility to anoxia. We found that loss of either nlp-40 or aex-2 decreased locomotor activity and reversal frequency early during 48 hours of anoxia, suggesting that nlp-40 and aex-2 are required for the proper execution of these behaviors. We found that neuronal knockdown of nlp-40 recapitulated the behaviors observed in nlp-40 mutant animals and increased survival; however, restoring aex-2 function in glr-1 interneurons or motor neurons was sufficient to rescue behaviors to wild-type and restore vulnerability to anoxia. Conclusions: Overall, our results suggest that NLP-40 and AEX-2 likely function in cholinergic or glr-1 interneurons or motor neurons to regulate escape behaviors during anoxia. Escape behaviors are part of the homeostatic response and are typically protective in the wild; however, in our paradigm, we show that loss of either nlp-40 or aex-2 reduces escape responses and confers protection against 48 hours of anoxia. Collectively, these results highlight a new role for NLP-40 and AEX-2 in anoxia and shed light on mechanisms underlying the adaptive responses to anoxia.

neuroscience↗

bioRxiv2026

Meta-analysis of Genes and Pathways that Protect Against Hypoxia.

Oxygen is essential for all terrestrial animals, but there is dramatic variability in how well different animals and even different cell types can adapt to reduced oxygen availability. We used a meta-analysis of the literature, with a focus on mouse studies, to identify pathways that might act to protect animals in low oxygen environments. We identified 108 genes whose mRNA levels change under hypoxia, and 55 genes critical for mounting a response to hypoxia. With this data, we developed a list of conserved genes, and we tested three C.elegans genes previously uncharacterized in hypoxia, mxl-3, yap-1, and ador-1, and found that loss of function altered egg-laying during and after hypoxia. Our method provides a more targeted approach of how to screen for hypoxic phenotypes and study in more genetically tractable organisms to show mechanisms.

genetics↗

bioRxiv2023

Pseudomonas aeruginosa shows between and within strains heterogeneity in virulence phenotype after passive exposure to zebrafish (Danio rerio) and nematodes (Caenorhabditis elegans)

The rapid emergence of diseases and parasites in aquatic wildlife requires improved methodologies to identify and characterize new and future pathogens. While microinjection of pathogens directly into a sentinel organism such as zebrafish enables the exploration of infection and immune response in the host, such methodology focuses primarily on identifying causative agents in events of aquatic wildlife mortality due to acute infection. Here, we present an updated protocol of infection by static immersion in larval zebrafish to investigate the possible effect of prolonged environmental exposure to an opportunistic pathogen. By controlling microbial growth and monitoring mortality over five days, we show that static immersion can detect minute differences in virulence profiles between and within different strains of Pseudomonas aeruginosa, an important opportunistic pathogen of animals and humans. We then conducted two sets of passive exposure virulence assays in Caenorhabditis elegans, an alternative model. We demonstrated the virulence phenotype, while showing slight differences between experimental models, showed similar trends. We believe that passive exposure thus offers a practical host-pathogen model that simulates opportunistic infection occurring in the environment and enables the detection of minute changes in virulence between and within bacterial strains.

microbiology↗

bioRxiv2020

Preconditioning of Caenorhabditis elegans to Anoxic Insult by Inactivation of Cholinergic, GABAergic, and Muscle Activity

For most metazoans, oxygen deprivation leads to cell dysfunction and if severe, death. Sublethal stress prior to a hypoxic or anoxic insult ("preconditioning") 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 preconditioning 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 organisms response to anoxia.

neuroscience↗