Morrison GE et al. (1999) Behav Neurosci "Olfactory associative learning in Caenorhabditis elegans is impaired in lrn-1 and lrn-2 mutants."

Runciman S, van der Kooy D, Wen JYM, Morrison GE

[Behav Neurosci, 1999]

The C. elegans mutants, lrn-1 and lrn-2, are impaired in associative learning using conditioned taste cues. Both mutants are defective in associative learning about appetitive and aversive events, indicating that lrn-1 and lrn-2 exert effects across motivational boundaries. In a new olfactory associative learning paradigm, in which wild type worms learn to avoid a previously attractive diacetyl odor after it has been paired with an aversive acetic acid solution, lrn-1 and lrn-2 are impaired. Although defective in associative learning using a conditioned olfactory cue, nonassociative learning (habituation and dishabituation) using this same olfactory cue is unaffected. The discovery that lrn-1 and lrn-2 are defective in associative learning with both taste and olfactory cues may suggest that associative learning in different sensory modalities converges on a common genetic pathway in C. elegans that is subserved by lrn-1 and lrn-2.

Morrison GE et al. (1995) International C. elegans Meeting "lrn-1 and lrn-2 Block Associative Learning in C. elegans."

Morrison GE, Wen JYM, Runciman S, Neghandi H, van der Kooy D, Kumar N

[International C. elegans Meeting, 1995]

The nematode C. elegans can be conditioned using a classical conditioning paradigm based on its chemotactic responses to the conditioning stimuli (CS), Na+ (NaCH3CHOO) and Cl- (NH4Cl), which are equally preferred under baseline conditions. After exposure to one of the CS ions (CS+) in the presence of the US (E. coli, a food source), counterbalanced by an equal exposure to the alternate ion (CS-) in the absence of the US, the animals demonstrate a significant preference for the CS+ ion on testing. Using an EMS screen, we isolated two lines of mutant animals (lrn-1 and lrn-2) that after conditioning displayed the equivalent preferences for the CS+ and CS- ions shown by unconditioned wild type worms. Using garlic (an aversive stimulus) as a US, wild type worms show a conditioned avoidance for the ion (CS+) that was paired with the garlic, whereas the two mutant lines displayed equivalent preferences for the CS+ and CS- ions after conditioning. We used a short-term assay to determine the effects of the two mutations on short- and long-term memory. After conditioning for minutes, the initial test headings (after 30 sec) of individual wild type animals towards the CS+ and CS- ions are not significantly different from the learning scores in our original, 90 min test paradigm (~75% approach to the CS+ ion). However, after conditioning, initial test headings of individual mutant animals remain balanced, 50% approaching the CS+ ion and 50% approaching the CS- ion. These two mutants are normal in motor and sensory capabilities since the approaches to point sources of both CS ions and the US (E. coli) are similar to those of wild type animals in both the accumulation rates and overall preferences. As well, the two mutants are capable of normal non-associative learning (habituation) to the ions used as conditioning stimuli in the associative learning paradigm. Using the sequence tagged site strategy for C. elegans and multiplex PCR techniques, we have begun mapping the two mutations through the generation of Bergerac/mutant N2 hybrids.

Morrison GE et al. (1997) International C. elegans Meeting "The Genetic Characterization of lrn-1 and lrn-2: Genes for Associative Learning in C. elegans."

van Kooy D, Nuttley WM, Runciman S, Morrison GE

[International C. elegans Meeting, 1997]

Using the multiplex PCR-based polymorphic sequence tagged site (STS) mapping strategy for C. elegans we mapped the two associative learning mutations to linkage groups; lrn-1 is on LGIII and lrn-2 is on LGII. The STS mapping strategy makes use of the transposable element Tc1, which is a source of easily identified and well distributed polymorphisms. The STSs, which act as dominant markers, are Tc1 transposon insertions, present at approximately 500 loci which are well distributed throughout the Bergerac strain RW7000, but absent from the Bristol N2 strain in which the two mutations have been isolated. Each STS has a unique PCR product that is easily resolved using standard gel electrophoresis. Mutant males were crossed with Bergerac hermaphrodites and the F2 progeny screened for associative learning abilities. Since both lrn-1 and lrn-2 are single recessive mutations, we expect that approximately 25% of the F2 generation will be homozygous for the selected learning mutation. Those individuals determined to be homozygous for the learning mutation based on behavioural data were separated onto individual plates and allowed to self. Once a sufficient number of eggs were laid, the F2 parent was picked from the plate for DNA analysis using standard multiplex PCR. The PCR 'cocktail' used for the multiplex PCR reaction contained the common Tc1 primer 618, and primers specific for a Tc1 on each nematode chromosome. The homozygous recessive nature of lrn-1 and lrn-2 requires that two copies of the mutant chromosome be inherited in order to show the non-learning phenotype, thus detection of the linked Tc1 will be a relatively rare event. Analysis of the STS inheritance pattern for the mutant/Bergerac hybrid animals revealed that the Tc1 for LGIII was present in 13% of the lrn-1/Bergerac F2 animals and the Tc1 for LGII was present in 13% of lrn-2/Bergerac F2 animals.

Morrison GE et al. (2001) Behav Neurosci "A mutation in the AMPA-type glutamate receptor, glr-1, blocks olfactory associative and nonassociative learning in Caenorhabditis elegans."

van der Kooy D, Morrison GE

[Behav Neurosci, 2001]

The alpha -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type ionotropic glutamate receptor mediates fast excitatory neurotransmission in the vertebrate brain and is important for synaptic plasticity and the initial induction of long-term potentiation (LTP). This study found that the putative Caenorhabditis elegans AMPA receptor gene. glr-1. plays a significant role in experience-dependent behavior in C. elegans. glr-1 mutants are deficient in an olfactory associative learning task, in which diacetyl (DA) is paired with acetic acid solution. glr-1 mutant nematodes are also impaired in nonassociative learning (habituation) with the same DA stimulus. The C elegans learning mutants, lrn-1 and lrn-2. are impaired in chemosensory associative learning yet have no deficits in habituation. The results suggest that although associative and nonassociative learning can be genetically dissociated (lrn-1 and lrn-2), they also share some common molecular processes, including glr-1-mediated neurotransmission.

Morrison GE et al. (1997) Behav Neurosci "Cold shock before associative conditioning blocks memory retrieval, but cold shock after conditioning blocks memory retention in Caenorhabditis elegans."

Morrison GE, van der Kooy D

[Behav Neurosci, 1997]

The effects of cooling on associative learning and memory processes in Caenorhabditis elegans were investigated by giving the worms cold shock at various times before or after conditioning. A pretraining cold shock in the 30 min immediately before conditioning and a posttraining cold shock in the 30 min immediately after conditioning both disrupted learning and memory processes tested a short time after conditioning. However, if tested 3 hr after conditioning, worms given a pretraining cold shock demonstrated learned preferences, whereas worms given a posttraining cold shock still had memory deficits. These results suggest that the effects of cold shock on associative learning and memory can be dissociated into effects on memory retrieval and memory retention.

GE Morrison et al. (1999) International C. elegans Meeting "Mutations in the AMPA-type glutamate receptor, glr-1, block olfactory associative and non-associative learning in C. elegans."

GE Morrison, D van der Kooy

[International C. elegans Meeting, 1999]

The AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionate) type ionotropic glutatmate receptor mediates fast excitatory neurotransmission in the vertebrate brain and is important for synaptic plasticity and the initial induction of long-term potentiation (LTP). Neurotransmission through glutamate also occurs in C. elegans . The putative C. elegans AMPA receptor gene, glr-1 , is expressed in the post-synaptic targets of the ASH sensory neuron and plays a role in mechanosensory avoidance but not osmotic avoidance, two behaviours mediated by ASH. Here we show that neurotransmission through glr-1 plays a significant role in experience-dependent behaviour in C. elegans . glr-1 mutant worms are deficient in olfactory associative learning in which worms learn not to track the previously attractive conditioned cue, diacetyl (DA), after it has been paired with an aversive acetic acid (AA) solution. glr-1 mutant worms acutely sense and respond to DA and AA just as wild type worms do, yet are unable to form an association between the two stimuli. Moreover, glr-1 mutant worms are impaired in non-associative learning (habituation) after long exposures to the same DA stimulus. The C. elegans learning mutants, lrn-1 and lrn-2 , are impaired in chemosensory associative learning and have no deficits in habituation. The results suggest that although associative and non-associative learning can be genetically dissociated ( lrn-1 and lrn-2 ) they also share some common molecular processes including glr-1 .

Xu T et al. (2022) Food Funct "Longevity-promoting properties of ginger extract in Caenorhabditis elegans via the insulin/IGF-1 signaling pathway."

Tao M, Pan S, Xu T, Wu T, Li R, Xu X

[Food Funct, 2022]

Ginger is a traditional medicinal and edible plant with multiple health-promoting properties. Nevertheless, the effects and potential mechanism of ginger on antiaging remain unknown. The aim of this study was to comprehend the antiaging effects and potential mechanism of ginger in Caenorhabditis elegans (C. elegans). The current findings showed that the lifespan of C. elegans was prolonged by 23.16% with the supplementation of 60 μg mL-1 ginger extract (GE), and the extension of lifespan was mainly attributed to the major bioactive compounds in GE, 6-, 8-, 10-gingerol and 6-, 8-, 10-shogaol. Subsequently, GE promoted healthy aging by improving nematode movement and attenuating lipofuscin accumulation, and enhanced stress tolerance by up-regulating the expression of stress-related genes and activating DAF-16 and SKN-1. Moreover, lifespan assays of relative mutants revealed that GE mediated extension of lifespan via the insulin/IGF-1 signaling (IIS) pathway. In summary, GE endowed nematodes (C. elegans) with longevity and stress resistance in an IIS pathway dependent manner.

Aranaz P et al. (2021) Nutrients "Grifola frondosa (Maitake) Extract Reduces Fat Accumulation and Improves Health Span in C. elegans through the DAF-16/FOXO and SKN-1/NRF2 Signalling Pathways."

Vettorazzi A, Fabra MJ, Aranaz P, Pena A, Castellari M, Parlade J, Gonzalez-Navarro CJ, Pera J, Martinez-Abad A, Milagro FI, Lopez-Rubio A

[Nutrients, 2021]

In recent years, food ingredients rich in bioactive compounds have emerged as candidates to prevent excess adiposity and other metabolic complications characteristic of obesity, such as low-grade inflammation and oxidative status. Among them, fungi have gained popularity for their high polysaccharide content and other bioactive components with beneficial activities. Here, we use the <i>C. elegans</i> model to investigate the potential activities of a <i>Grifola frondosa</i> extract (GE), together with the underlying mechanisms of action. Our study revealed that GE represents an important source of polysaccharides and phenolic compounds with in vitro antioxidant activity. Treatment with our GE extract, which was found to be nongenotoxic through a <i>SOS/umu</i> test, significantly reduced the fat content of <i>C. elegans</i>, decreased the production of intracellular ROS and aging-lipofuscin pigment, and increased the lifespan of nematodes. Gene expression and mutant analyses demonstrated that the in vivo anti-obesity and antioxidant activities of GE were mediated through the <i>daf-2/daf-16</i> and <i>skn-1/nrf-2</i> signalling pathways, respectively. Taken together, our results suggest that our GE extract could be considered a potential functional ingredient for the prevention of obesity-related disturbances.

Huang CH et al. (2015) J Nutr Biochem "Analysis of lifespan-promoting effect of garlic extract by an integrated metabolo-proteomics approach."

Hsu FY, Wu YH, Liang SS, Kuo CJ, Hsu AL, Chiou SH, Huang CH, Zhong L, Tseng MY

[J Nutr Biochem, 2015]

The beneficial effects of garlic (Allium sativum) consumption in treating human diseases have been reported worldwide over a long period of human history. The strong antioxidant effect of garlic extract (GE) has also recently been claimed to prevent cancer, thrombus formation, cardiovascular disease and some age-related maladies. Using Caenorhabditis elegans as a model organism, aqueous GE was herein shown to increase the expression of longevity-related FOXO transcription factor daf-16 and extend lifespan by 20%. By employing microarray and proteomics analysis on C. elegans treated with aqueous GE, we have systematically mapped 229 genes and 46 proteins with differential expression profiles, which included many metabolic enzymes and yolky egg vitellogenins. To investigate the garlic components functionally involved in longevity, an integrated metabolo-proteomics approach was employed to identify metabolites and protein components associated with treatment of aqueous GE. Among potential lifespan-promoting substances, mannose-binding lectin and N-acetylcysteine were found to increase daf-16 expression. Our study points to the fact that the lifespan-promoting effect of aqueous GE may entail the DAF-16-mediated signaling pathway. The result also highlights the utility of metabolo-proteomics for unraveling the complexity and intricacy involved in the metabolism of natural products in vivo.

Morita S et al. (2001) Physica A "Geometrical structure of the neuronal network of Caenorhabditis elegans."

Funabashi Y, Morita S, Oka K, Oshio K, Osana Y, Kawamura K

[Physica A, 2001]

The neuronal network of the soil nematode Caenorhabditis elegans (C. elegans), which is a good prototype for biological studies, is investigated. Here, the neuronal network is simplified as a graph. We use three indicators to characterize the graph; vertex degree, generalized eccentricity (GE), and complete subgraphs. The graph has the central part and the strong clustering structure. We present a simple model, which shows that the neuronal network has a high-dimensional geometrical structure.