Ju J et al. (2014) Int J Environ Res Public Health "Cyanobacterial xenobiotics as evaluated by a Caenorhabditis elegans neurotoxicity screening test."

Saul N, Yin L, Ju J, Pu Y, Kochan C, Steinberg CE, Putschew A

[Int J Environ Res Public Health, 2014]

In fresh waters cyanobacterial blooms can produce a variety of toxins, such as microcystin variants (MCs) and anatoxin-a (ANA). ANA is a well-known neurotoxin, whereas MCs are hepatotoxic and, to a lesser degree, also neurotoxic. Neurotoxicity applies especially to invertebrates lacking livers. Current standardized neurotoxicity screening methods use rats or mice. However, in order to minimize vertebrate animal experiments as well as experimental time and effort, many investigators have proposed the nematode Caenorhabditis elegans as an appropriate invertebrate model. Therefore, four known neurotoxic compounds (positive compounds: chlorpyrifos, abamectin, atropine, and acrylamide) were chosen to verify the expected impacts on autonomic (locomotion, feeding, defecation) and sensory (thermal, chemical, and mechanical sensory perception) functions in C. elegans. This study is another step towards successfully establishing C. elegans as an alternative neurotoxicity model. By using this protocol, anatoxin-a adversely affected locomotive behavior and pharyngeal pumping frequency and, most strongly, chemotactic and thermotactic behavior, whereas MC-LR impacted locomotion, pumping, and mechanical behavior, but not chemical sensory behavior. Environmental samples can also be screened in this simple and fast way for neurotoxic characteristics. The filtrate of a Microcystis aeruginosa culture, known for its hepatotoxicity, also displayed mild neurotoxicity (modulated short-term thermotaxis). These results show the suitability of this assay for environmental cyanotoxin-containing samples.

Ju J et al. (2014) Ecotoxicol Environ Saf "Neurotoxic evaluation of two organobromine model compounds and natural AOBr-containing surface water samples by a Caenorhabditis elegans test."

Saul N, Yin L, Baberschke N, Pu Y, Kochan C, Steinberg CE, Lieke T, Putschew A, Ju J

[Ecotoxicol Environ Saf, 2014]

Brominated organic compounds are known as disinfection byproducts. Very recently, however, even natural brominated organic compounds (analyzed as adsorbable organic bromine; AOBr) have been found in decaying freshwater cyanobacteria blooms. Among the identified compounds was dibromoacetic acid (DBAA), which has proven to be neurotoxic at rather high concentrations in mammalian assays. Currently it is open how single compounds as well as complex mixtures impact organisms at environmentally realistic concentrations. Furthermore, it is also unclear how natural organic matter, mainly humic substances (HS), which are present in all freshwater systems, modulates the toxic impact of AOBr. Therefore, two AOBr compounds (DBAA and tetrabromobisphenol-A; TBBP-A) and AOBr-containing water samples were tested using a Caenorhabditis elegans neurotoxicity assay that measured autonomic and sensory functions. TBBP-A had an impact on three response variables of C. elegans and can be classified neurotoxic. In contrast to our expectations, DBAA led to neurostimulation of two autonomic functions, but had a temporary impact on the defecation interval. All surface water samples contained measurable amounts of AOBr. Exposure of C. elegans to concentrated water samples - one in particular - increased three of the four locomotion traits and left defecation activity and both sensory variables unchanged. This stimulation might be due to unidentified compounds in the samples or to a hormetic effect of the AOBr compounds. Thermotactic behavior was characterized by a temporary preference for the colder environment, indicating a temporary mild neurotoxicity. Overall, the set of relative simple phenotypic tests used in the current study revealed a meaningful neurotoxic or neurostimulative profile in response to chemical compounds or natural samples. Furthermore, it shows that the resulting response to natural AOBr compounds at environmentally realistic concentrations was not necessarily adverse, but instead, that the mixtures of natural AOBr were neurostimulatory.

Menzel R et al. (2011) Environ Sci Technol "Enrichment of humic material with hydroxybenzene moieties intensifies its physiological effects on the nematode Caenorhabditis elegans."

Tiedt S, Menzel R, Bahrs H, Menzel S, Steinberg CE, StoBer R, Saul N, Kubsch G, Putschew A

[Environ Sci Technol, 2011]

Dissolved humic substances are taken up by organisms and interact on various molecular and biochemical levels. In the nematode Caenorhabditis elegans, such material can promote longevity and increase its reproductive capacity; moreover, the worms tend to stay for longer in humic-enriched environments. Here, we tested the hypothesis that the chemical enrichment of humic substances with hydroxybenzene moieties intensifies these physiological effects. Based on the leonardite humic acid HuminFeed (HF), we followed a polycondensation reaction in which this natural humic substance and a dihydroxybenzene (hydroquinone or benzoquinone) served as reaction partners. Several analytical methods showed the formation of the corresponding copolymers. The chemical modification boosted the antioxidant properties of HF both in vitro and in vivo. Humic substances enriched with hydroxybenzene moieties caused a significantly increased tolerance to thermal stress in C. elegans and extended its lifespan. Exposed nematodes showed delayed linear growth and onset of reproduction and a stronger pumping activity of the pharynx. Thus, treated nematodes act younger than they really are. In this feature the modified HF replicated the biological impact of hydroquinone-homopolymers and various plant polyphenol monomers, thereby supporting the hydroxybenzene moieties of humic substances as major effective structures for the physiological effects observed in C. elegans.

Saul N et al. (2015) Environ Sci Pollut Res Int "Adsorbable organic bromine compounds (AOBr) in aquatic samples: a nematode-based toxicogenomic assessment of the exposure hazard."

Putschew A, Lieke T, Kochan C, Baberschke N, Saul N, Menzel R, Chakrabarti S, Steinberg CE, Sturzenbaum SR

[Environ Sci Pollut Res Int, 2015]

Elevated levels of adsorbable organic bromine compounds (AOBr) have been detected in German lakes, and cyanobacteria like Microcystis, which are known for the synthesis of microcystins, are one of the main producers of natural organobromines. However, very little is known about how environmental realistic concentrations of organobromines impact invertebrates. Here, the nematode Caenorhabditis elegans was exposed to AOBr-containing surface water samples and to a Microcystis aeruginosa-enriched batch culture (MC-BA) and compared to single organobromines and microcystin-LR exposures. Stimulatory effects were observed in certain life trait variables, which were particularly pronounced in nematodes exposed to MC-BA. A whole genome DNA-microarray revealed that MC-BA led to the differential expression of more than 2000 genes, many of which are known to be involved in metabolic, neurologic, and morphologic processes. Moreover, the upregulation of cyp- and the downregulation of abu-genes suggested the presence of chronic stress. However, the nematodes were not marked by negative phenotypic responses. The observed difference in MC-BA and microcystin-LR (which impacted lifespan, growth, and reproduction) exposed nematodes was hypothesized to be likely due to other compounds within the batch culture. Most likely, the exposure to low concentrations of organobromines appears to buffer the effects of toxic substances, like microcystin-LR.

Quartey MO et al. (2021) Sci Rep "The A(1-38) peptide is a negative regulator of the A(1-42) peptide implicated in Alzheimer disease progression."

Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO

[Sci Rep, 2021]

The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).

Danielle Thierry-Mieg et al. (2003) Worm Breeder's Gazette "www.wormgenes.org , a new gene centered database"

Vahan Simonyan, Michel Potdevin, Mark Sienkiewicz, Yuji KOHARA, Jean Thierry-Mieg, Danielle Thierry-Mieg, Tadasu SHIN-I

[Worm Breeder's Gazette, 2003]

Wormgenes is a new resource for C.elegans offering a detailed summary about each gene and a powerful query system.

Tangrodchanapong T et al. (2020) Front Pharmacol "Frondoside A Attenuates Amyloid- Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation."

Tangrodchanapong T, Sobhon P, Meemon K

[Front Pharmacol, 2020]

Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.

Hodgkin JA (1998) International Journal of Developmental Biology "Seven types of pleiotropy."

Hodgkin JA

[International Journal of Developmental Biology, 1998]

Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.

Tuck S (2011) Curr Biol "Extracellular vesicles: budding regulated by a phosphatidylethanolamine translocase."

Tuck S

[Curr Biol, 2011]

Recent work on a Caenorhabditis elegans transmembrane ATPase reveals a central role for the aminophospholipid phosphatidylethanolamine in the production of a class of extracellular vesicles.

Viney ME et al. (2004) Naturwissenschaften "Is dauer pheromone of Caenorhabditis elegans really a pheromone?"

Viney ME, Franks NR

[Naturwissenschaften, 2004]

Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.