Assessment of developmental neurotoxicology-associated alterations in neuronal architecture and function usingCaenorhabditis elegans

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Few of the many chemicals that regulatory agencies are charged with assessing for risk have been carefully tested developmental neurotoxicity (DNT). To speed up testing efforts, as well to reduce use vertebrate animals, great effort is being devoted alternate laboratory models DNT. A major mechanism DNT altered neuronal architecture resulting from chemical exposure during neurodevelopment. Caenorhabditis elegans a nematode has extensively studied by neurobiologists and biologists, lesser extent neurotoxicologists. The trajectory nervous system in C. easily visualized, normally entirely invariant, fully mapped. Therefore, we hypothesized could be powerful vivo model test potential alter patterning architecture. whether this might true, developed novel paradigm includes throughout development, examines all neurotransmitter types architectural alterations, tests behaviors specific dopaminergic, cholinergic, glutamatergic functions. We used characterize effects early-life exposures neurotoxicants lead, cadmium, benzo(a)pyrene (BaP) on also assessed would specification expression reporter genes diagnostic neurotransmitters. identified no cases which apparent type neurons examined changed, but morphology was altered. found neuron-specific were mid-adulthood populations measured morphological neurodegeneration earlier stages. functional changes consistent observed terms neuron affected. those reported mammalian literature, strengthening case model, made observations should followed future studies.

Язык: Английский

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Gene regulatory mechanisms underlying evolutionary adaptations of homologous neuronal cell types

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Summary How nervous systems coordinate the generation of specific neuron types with gene expression plasticity and how these mechanisms impact cell type evolution is unknown. Here we use Caenorhabditis species to study neuron-type robustness, evolution, using VC4 VC5 cholinergic motoneurons as models. In C. elegans , found that epigenetic silencing through histone 3 lysine 9 methylation (H3K9me) necessary suppress serotonin reuptake mod-5/ Sert a serotonergic phenotype in cells. contrast, observed neurons Angaria group genus have evolved an intense staining. This caused by emergence new enhancer locus, which has been recruited ancestral regulatory network. Enhancer transfer from angaria sufficient impose constitutive fate . Remarkably, acquiring this trait modulates egg-laying responses high levels exogenous serotonin, can be environments. Finally, discovered repression indeed plastic adjusted environmental growth conditions elicit behaviours similar those species. Our work identifies robust neuron-type-specific programs responses. These findings identify framework underlying features novel behaviours.

Язык: Английский

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Behavioral adaptations of Caenorhabditis elegans against pathogenic threats

PeerJ, Год журнала: 2025, Номер 13, С. e19294 - e19294

Опубликована: Апрель 14, 2025

This review examines the behavioral adaptation mechanisms of Caenorhabditis elegans in response to pathogenic bacterial threats, emphasizing their ecological significance. It systematically explores how such as avoidance behavior, transgenerational learning, and forgetting enable C. optimize its survival reproductive strategies within dynamic microbial environments. detects harmful signals through chemosensation initiates behaviors. Simultaneously, it manages environmental energy allocation memory forgetting, allowing cope with selective pressures from fluctuations. In contrast, bacteria Pseudomonas aeruginosa Salmonella influence behavior toxin release biofilm formation, highlighting complex co-evolutionary dynamics between hosts pathogens. Additionally, these pathogens employ “Trojan Horse-like” “Worm Star” kill , further complicating host-pathogen interactions. These processes are driven by adaptations, biochemical signaling, evolutionary pressures, which emphasize niche ecosystems. serves a valuable model for studying study provides crucial theoretical insights into adaptive evolution ecosystem dynamics, offering guidance development biocontrol effective management

Язык: Английский

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Single-Nucleus Neuronal Transcriptional Profiling of MaleC. elegansUncovers Regulators of Sex-Specific and Sex-Shared Behaviors

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Summary Sexual differentiation of the nervous system causes differences in neuroanatomy, synaptic connectivity, and physiology. These sexually-dimorphic phenotypes ultimately translate into profound behavioral differences. C. elegans’ two sexes, XO males XX hermaphrodites, demonstrate neurobiology behavior. However, neuron class sex-specific transcriptomic differences, particularly at single-neuron level, that cause such phenotypic divergence remains understudied. Here, using single-nucleus RNA sequencing, we assessed compared adult male hermaphrodite elegans neuronal transcriptomes, identifying neurons, including previously-unannotated neurons. Sex-shared neurons displayed large expression with some classes clustering as distinct between sexes. Males express ∼100 male-specific GPCRs, largely limited to a subset We identified most highly-divergent functionally characterized sex-shared target, vhp-1, pheromone chemotaxis. Our data provide resource for discovering nervous-system-wide sex molecular basis behaviors.

Язык: Английский

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