Shen L et al. (2009) Environ Toxicol Pharmacol "Toxicity evaluation in nematode Caenorhabditis elegans after chronic metal exposure."

Wang D, Shen L, Ye H, Xiao J

[Environ Toxicol Pharmacol, 2009]

In this study, specific developmental stage for adults from day 1 to day 10 was selected to evaluate the chronic metal toxicity, because the population of dead nematodes and the accumulation of intestinal autofluorescence increased sharply after day 10. Chronic exposure to Cr, Pb, Cu, and Hg caused a significant elevation in fractions of dead animals after day 4, and resulted in a significant induction of hsp-16.2::gfp expression at all assayed metal concentrations. Moreover, chronic exposure to Ag, Cr, Pb, Cu, Hg, and Cd would induce a more severe stress response than exposure to Zn and Mn in intestine, and chronic exposure to Pb, Hg, Cr, Zn, and Mn would induce a more severe stress response than exposure to Ag, Cu and Cd in head neurons. Therefore, in determining the usefulness of animals in metal toxicity assessment, this study established a method using nematodes in testing the chronic metal toxicity.

Shen L et al. (2010) Mech Ageing Dev "Regulation of longevity by genes required for the functions of AIY interneuron in nematode Caenorhabditis elegans."

Cai T, Lin X, Wang D, Shen L, Hu Y

[Mech Ageing Dev, 2010]

In Caenorhabditis elegans, functional ttx-3, sra-11, ceh-10, and ceh-23 genes are required for the functions of AIY interneuron. Compared to wild-type N2, mutations in ttx-3 and ceh-10 significantly decreased lifespan, whereas mutations in sra-11 and ceh-23 did not obviously influence nematode lifespan. Mutations in ttx-3 and ceh-10 were associated closely with lower pumping rates at adult day 8 and caused a more rapid accumulated intestinal autofluorescence than wild-type N2. Mutations in ceh-10 remarkably affected fertility and egg number in the uterus. The regulation of ttx-3 and ceh-10 on longevity was not temperature-dependent, and ttx-3, and ceh-10 mutants all formed very few dauers at 27C. The shortened lifespan of the ttx-3 or ceh-10 mutants was completely or largely rescued by expression of TTX-3 or CEH-10 in AIY interneurons. Moreover, the long-lived phenotype of the daf-2 mutant could be suppressed by both the ttx-3 and the ceh-10 mutations. Furthermore, ablation of AIY interneurons shortened the longevity of wild-type and the daf-2 mutant. Therefore, ttx-3 and ceh-10 regulate the longevity through influencing the insulin/IGF signaling pathway in C. elegans.

Shen L et al. (2020) Biochim Biophys Acta Mol Basis Dis "TDP-1/TDP-43 potentiates human -Synuclein (HASN) neurodegeneration in Caenorhabditis elegans."

Leung KL, Wang C, Lakso M, Wong G, Chen L, Lo E, Shen L

[Biochim Biophys Acta Mol Basis Dis, 2020]

TAR DNA binding protein (TDP-43) is a DNA/RNA binding protein whose pathological role in amyotrophic lateral sclerosis (ALS) and frontal temporal lobe dementia (FTLD) via formation of protein aggregates is well established. In contrast, knowledge concerning its interactions with other neuropathological aggregating proteins is poorly understood. Human -synuclein (HASN) elicits dopaminergic neuron degeneration via protein aggregation in Parkinson's disease. HASN protein aggregates are also found in TDP-43 lesions and colocalize in Lewy Body Dementia (LBD). To better understand the interactions of TDP-43 and HASN, we investigated the effects of genetic deletion of tdp-1, the Caenorhabditis elegans ortholog of human TDP-43, as well as overexpression of TDP-43, in transgenic models overexpressing HASN^WT and HASN^A53T. Tdp-1 deletion improved the posture, movement, and developmental delay observed in transgenic animals pan-neuronally overexpressing HASN^A53T, and attenuated the loss and impairment of dopaminergic neurons caused by HASN^A53T or HASN^WT overexpression. Tdp-1 deletion also led to a decrease in protein level, mRNA level and aggregate formation of HASN in living animals. RNA-seq studies suggested that tdp-1 supports expression of lysosomal genes and decreases expression of genes involved in heat shock. RNAi demonstrated that heat shock proteins can mediate HASN neuropathology. Co-overexpression of both human TDP-43 and HASN^WT resulted in locomotion deficits, shorter lifespan, and more severe dopaminergic neuron impairments compared to single transgenes. Our results suggest TDP-1/TDP-43 potentiates HASN mediated neurodegeneration in C. elegans. This study indicates a multifunctional role for TDP-1/TDP-43 in neurodegeneration involving HASN.

Shen L et al. (2021) Front Neurosci "Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Caenorhabditis elegans Parkinson's Disease Model Overexpressing Human -Synuclein and Influence of tdp-1."

Shen L, Wong G, Chen L, Wang C

[Front Neurosci, 2021]

MicroRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) regulate gene expression and biological processes through specific genetic and epigenetic mechanisms. Recent studies have described a dysregulation of small non-coding RNAs in Parkinson's disease (PD) tissues but have been limited in scope. Here, we extend these studies by comparing the dysregulation of both miRNAs and piRNAs from transgenic <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) nematodes overexpressing pan-neuronally human -synuclein wild-type (WT) (HASN^WT OX) or mutant (HASN^A53T OX). We observed 32 miRNAs and 112 piRNAs dysregulated in HASN^A53T OX compared with WT. Genetic crosses of HASN^A53T OX PD animal models with <i>tdp-1</i> null mutants, the <i>C. elegans</i> ortholog of TDP-43, an RNA-binding protein aggregated in frontal temporal lobar degeneration, improved their behavioral deficits and changed the number of dysregulated miRNAs to 11 and piRNAs to none. Neuronal function-related genes <i>T28F4.5</i>, <i>C34F6.1</i>, <i>C05C10.3</i>, <i>camt-1</i>, and <i>F54D10.3</i> were predicted to be targeted by cel-miR-1018, cel-miR-355-5p (<i>C34F6.1</i> and <i>C05C10.3</i>), cel-miR-800-3p, and 21ur-1581 accordingly. This study provides a molecular landscape of small non-coding RNA dysregulation in an animal model that provides insight into the epigenetic changes, molecular processes, and interactions that occur during PD-associated neurodegenerative disorders.

Svendsen JM et al. (2018) Dev Cell "piRNA Rules of Engagement."

Svendsen JM, Montgomery TA

[Dev Cell, 2018]

piRNAs are known to silence transposable elements, but not all piRNAs match transposon sequences. Recent studies from Shen etal. (2018) and Zhang etal. (2018) identify rules for piRNA target recognition in Caenorhabditis elegans. Permissive pairing rules allow targeting of essentially all germline mRNAs, while protective mechanisms prevent silencing self-genes.

Forrester S et al. (2007) Foodborne Pathog Dis "Evaluation of the pathogenicity of Listeria spp. in Caenorhabditis elegans."

Schwab U, Wiedmann M, Hoose WA, Milillo SR, Forrester S

[Foodborne Pathog Dis, 2007]

Caenorhabditis has proven to be a useful model for studying host-pathogen interactions as well as the ability of nematodes to serve as vectors for the dispersal of foodborne pathogens. In this study, we evaluated whether C. elegans can serve as a host for Listeria spp. While there was an effect of growth media on C. elegans killing, C. elegans exposed to L. monocytogenes and L. innocua pregrown in Luria-Bertani medium showed reduced survival when compared to nonpathogenic E. coli OP50, while L. seeligeri showed survival similar to E. coli OP50. In a preference assay, C. elegans preferred E. coli over L. monocytogenes and L. innocua, but showed no preference between L. monocytogenes and L. innocua. A gentamicin assay indicated that L. monocytogenes did not persist within the C. elegans intestinal tract. Our findings that L. monocytogenes and L. innocua strains tested have equally deleterious effects on C. elegans and that L. monocytogenes did not establish intestinal infection conflict with other recently published results, which found intestinal infection and killing of C. elegans by L. monocytogenes. Further studies are thus needed to clarify the interactions between L. monocytogenes and C. elegans, including effects of environmental conditions and strain differences on killing and intestinal infection.

Abraham D et al. (1989) Am J Trop Med Hyg "Immunity to larval Brugia malayi in BALB/c mice: protective immunity and inhibition of larval development."

Grieve RB, Christensen BM, Abraham D, Holy JM

[Am J Trop Med Hyg, 1989]

The objective of this study was to analyze the immune response of mice to the larval stages of Brugia malayi. Male BALB/c mice were inoculated with 3 doses of irradiated third-stage larvae (L-3) of B. malayi and were subsequently challenged with L-3 implanted ip within diffusion chambers. After 3 weeks, larvae were recovered to determine their viability, length, and stage of development. A significant reduction in parasite survival was observed in immunized mice. Furthermore, larvae recovered from immunized mice were significantly shorter than larvae recovered from control mice. All larvae recovered from immunized mice were L-3, whereas 96% of larvae recovered from controls were fourth-stage larvae (L-4). Sera collected from control and immunized mice were tested for the presence of antibodies reactive with L-3 and L-4 antigens using an indirect fluorescent antibody assay employing frozen larval cross-sections as antigen. Sera recovered after challenge of control mice reacted with internal, but not surface, antigens of L-3 and L-4. Alternatively, sera from immunized mice reacted with both internal and external antigens of both L-3 and L-4.

Sese BT et al. (2009) J Toxicol Environ Health A "Toxicity of polycyclic aromatic hydrocarbons to the nematode Caenorhabditis elegans."

Reid BJ, Grant A, Sese BT

[J Toxicol Environ Health A, 2009]

The presence of polycyclic aromatic hydrocarbons (PAHs) in the environment has attracted much concern owing to their mutagenic and carcinogenic properties. Regulatory authorities have favored the use of biological indicators as an essential means of assessing potential toxicity of environmental pollutants. This study aimed to assess the toxicity of acenaphthene, phenanthrene, anthracene, fluoranthene, pyrene, and benzo[a]pyrene to Caenorhabditis elegans by measuring LC50 and EC50 values for growth and reproduction. The exposure to all chemicals was carried out in aqueous medium. All PAHs showed a low acute toxicity to C. elegans. There was no significant mortality in C. elegans after 24 h of exposure at PAH concentrations within (and indeed above) their respective solubility limits. Prolonged exposure (72 h) at high concentrations for acenaphthene (70,573 microg/L), phenanthrene (3758 microg/L), anthracene (1600 microg/L), fluoranthene (1955 microg/L), pyrene (1653 microg/L), and benzo[a]pyrene (80 microg/L) produced mortality. Results also showed that reproduction and growth were much more sensitive parameters of adverse response than lethality, and consequently may be more useful in assessing PAH toxicity using C. elegans. In comparison with previous studies, C. elegans was found to be approximately 2-fold less sensitive to acenaphthene, 5-fold less sensitive to phenanthrene, and 20-fold less sensitive to fluoranthene than Daphnia magna. However, the 48-h LC50 for benzo[a]pyrene (174 microg/L) reported in the present study with C. elegans was similar to that reported elsewhere for Daphnia magna (200 microg/L). Although C. elegans indicated greater sensitivity to benzo[a]pyrene than Artemia salina (174 microg/L vs. 10000 microg/L), the organism showed less sensitivity to pyrene (8 microg/L vs. 2418 microg/L), fluoranthene (40 microg/L vs. 2719 microg/L), and phenanthrene (677 microg/L vs. 4772 microg/L) than Artemia salina. Caenorhabditis elegans, while not the most sensitive of species for PAH toxicity assessment, may still hold applicability in screening of contaminated soils and sediments.

Manalo RVM et al. (2020) Pharm Biol "Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson's disease."

Medina PMB, Manalo RVM

[Pharm Biol, 2020]

CONTEXT: L-DOPA is the first-line drug for Parkinson's disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. OBJECTIVES: (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. MATERIALS AND METHODS: =20). Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60mM), caffeine (10mM) or 60mM L-DOPA + 10 or 20mM caffeine (60LC10 and 60LC20) treatments were scored for 3days. RESULTS: Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.

Buyannemekh K et al. (2024) Dev Biol "Left/right asymmetrically expressed ephrin and Flamingo proteins regulate lateralized axon growth in C. elegans."

Buyannemekh K, Bertrand V, Villoutreix P

[Dev Biol, 2024]

While the nervous system of bilaterian animals is mainly left-right (L-R) symmetric at the anatomical level, some molecular and functional L-R asymmetries exist. However, the extent of these molecular asymmetries and their functional consequences remain poorly characterized. C. elegans allows to study L-R asymmetries in the nervous system with single-neuron resolution. We have previously shown that a neural bHLH transcription factor, HLH-16/Olig, is L-R asymmetrically expressed in the AIY neuron lineage and regulates AIY axon projections in a L-R asymmetric manner. Here, by combining a candidate approach and single-cell RNA sequencing data analysis, we identify the ephrin protein EFN-2 and the Flamingo protein FMI-1 as downstream targets of HLH-16 that are L-R asymmetrically expressed in the AIY lineage. We show that EFN-2 and FMI-1 collaborate in the L-R asymmetric regulation of axonal growth. EFN-2 may act via a non-canonical receptor of the L1CAM family, SAX-7. Our study reveals novel molecular L-R asymmetries in the C. elegans nervous system and their functional consequences.