Apart from the liver disruption, embryotoxicity and genotoxicity, microcystin （MC）-LR also could cause neurotoxicity. Nematode Caenorhabditis elegans was explored as a model to study the neurotoxicity. In the present study, we provided evidence to indicate the neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure to C. elegans. As a result, higher concentrations of MC-LR caused significantly severe defects of chemotaxis to NaCl and diacetyl, and thermotaxis. The neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure might be largely mediated by the damage on the corresponding sensory neurons （ASE, AWA, and AFD） and interneuron AIY. The expression levels ofche-1 and odr-7 were significantly decreased （P 〈 0.01） in animals exposed to MC-LR at concentrations lower than 10 μg/L, whereas the expression levels of ttx-1 and ttx-3 could be significantly （P 〈 0.01） lowered in animals even exposed to 1 μg/L of MC-LR. Moreover, both the chemotaxis to NaCl and diacetyl and the thermotaxis were more significantly reduced in MC-LR exposed mutants of che-1（p674）, odr-7（ky4）, ttx-1（p767）, and ttx-3（ks5） than those in exposed wild-type N2 animals at the same concentrations.
LI YunhuiYE HuayueDU MinZHANG YanfenYE BopingPU YuepuWANG Dayong
Objective To study the role of HLB-1 in regulating the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans. Methods To evaluate the functions of HLB-1 in regulating the organization and function of neuromuscular junctions, effects of hlb-1 mutation on the synaptic structures were revealed by uncovering the expression patterns of SNB-1 ：：GFP and UNC-49：GFP, and pharmacologic assays with aldicarb and levamisole were also used to test the synaptic functions. Further rescue and mosaic analysis confirmed HLB-1＇s role in regulating the organization and function of neuromuscular junctions. Results Loss of HLB-1 function did not result in defects in neuronal outgrowth or neuronal loss, but caused obvious defects of SNB-1：：GFP and UNC-49：：GFP puncta localization, suggesting the altered presynaptic and postsynaptic structures. The mutant animals exhibited severe defects in locomotion behaviors and altered responses to an inhibitor of acetylcholinesterase and a cholinergic agonist, indicating the altered presynaptic and postsynaptic functions. Rescue and mosaic analysis experiments suggested that HLB-1 regulated synaptic functions in a cell nonautonomously way. Moreover, HLB- 1 expression was not required for the presynaptic active zone morphology. Genetic evidence further demonstrated that hlb-1 acted in a parallel pathway with syd-2 to regulate the synaptic functions. Conclusion HLB-1 appeared as a new regulator for the organization and function of neuromuscular junctions in C. elegans.
Objective To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans （C. elegans）. Methods The mutants that had loss-of-function mutation of the genes required for AWA, AWC, ASE, and AFD sensory neurons were employed. Lifespan, the speed of pharynx pumping, the intestinal autofluorescence, the dauer formation, and the brood size were examined. Rescue experiments were performed to confrm the role of the genes required for the functions of AWA neuron in regulating lifespan. Moreover, genetic interactions between genes required for the functions of AWA neuron and insulin/ IGF signaling were investigated. Results Mutations of odr-7, odr-2, and odr-3 genes required for the functions of AWA neuron significantly increased the mean lifespan of nematodes and slowed the accumulation of intestinal autofluorescence. Besides, these mutations were closely associated with higher pumping rates during aging. However, mutation of odr-7, odr- 2, or odr-3 did not obviously affect the brood size or the dauer formation, and the regulation of longevity by odr-7, odr-2, and odr-3 was temperature-independent. In contrast, mutations of genes required for the functions of ASE, AWC, and AFD sensory neurons did not infuence the nematode lifespan. Moreover, expression of odr-7, odr-2 and odr-3 in AWA neuron could completely or largely restore the altered lifespan in odr-7, odr-2 and odr-3 mutants. Furthermore, genetic interaction assay demonstrated that the extended lifespan in odr-7 mutant could be suppressed by daf-16 mutation and enhanced by daf- 2 or age-1 mutation, whereas mev-1 and pha-4 were not required for the long lifespan of odr-7 mutant. Conclusion The genes required for the function of AWA sensory neuron could regulate the nematode longevity in an insulin/IGF signaling-dependent fashion in C. elegans.
Objective To investigate whether genes required for synaptogenesis and synaptic function are also involved in fat storage control in Caenorhabditis elegans. Methods Fat storage was examined in mutants of genes affecting the synaptogenesis and synaptic function. In addition, the genetic interactions of SNAREs syntaxin/unc-64 and SNAP-25/ric-4 with daf-2, daf-7, nhr-49, sbp-1 and mdt-15 in regulating fat storage were further investigated. The tissue-specific activities of unc-64 and ric-4 were investigated to study the roles of unc-64 and ric-4 in regulating fat storage in the nervous system and/or the intestine. Results Mutations of genes required for the formation of presynaptic neurotransmission site did not obviously influence fat storage. However, among the genes required for synaptic function, the plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 genes were involved in the fat storage control. Fat storage in the intestinal cells was dramatically increased in unc-64 and ric-4 mutants as revealed by Sudan Black and Nile Red strainings, although the fat droplet size was not significantly changed. Moreover, in both the nervous system and the intestine, expression of unc-64 significantly inhibited the increase in fat storage observed in unc-64 mutant. And expression of ric-4 in the nervous system completely restored fat storage in ric-4 mutant. Genetic interaction assay further indicated that both unc-64 and ric-4 regulated fat storage independently of daf-2 [encoding an insulin-like growth factor-I （IGF-I） receptor], daf-7 [encoding a transforming growth factor-β （TGF-β） ligand], and nhr-49 （encoding a nuclear hormone receptor）. Besides, mutation of daf-16 did not obviously affect the phenotype of increased fat storage in unc-64 or ric-4 mutant. Furthermore, unc-64 and ric-4 regulated fat storage probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways. In addition, fat storage in unc-64; ric-4 was higher than that in either unc-64 or ric-4 single mutant nema
Toxicity identification evaluation (TIE) can be used to determine the specific toxicant(s) in industrial effluents.In the current study,the authors have attempted to combine the advantages of the model organism,Caenorhabditis elegans,with the virtues of the TIE technique,to evaluate and identify the toxicity on aging from a paper recycling mill effluent.The results indicate that only the toxicities from mixed cellulose (MC) filtration and EDTA treatment are similar to the baseline aging toxicity,suggesting ...
We used toxicity identification evaluation （TIE） method to confirm the combinational effects of identified toxic metals in a paper recycling mill effluent in inducing the decreased lifespan in nematode Caenorhabditis elegans.Exposure to Ca ＋ Al caused more severely decreased lifespan than that exposed to Ca,or Al;and exposure to Ca ＋ Fe induced more severely decreased lifespan than that exposed to Ca,or Fe.Exposure to Ca＋Al＋Fe caused more severely decreased lifespan than that exposed to Ca,or Ca＋Fe.Moreover,the baseline toxicity on lifespan was doubled by doubling the concentration of combined metals （Ca＋Al＋Fe） in spiking test in original effluent （oe）,and lifespan defects in oe＋Ca＋Al＋Fe exposed nematodes were more severe than that in Ca＋Al＋Fe exposed nematode.Therefore,Ca＋Al＋Fe exposure may largely explain the formation of decreased lifespan induced by the examined industrial effluent.Furthermore,the observed reduction of lifespan induced by the combination of high level of Ca with other metals may be at least partially independent of the insulin-like pathway.
Dayong Wang,Yang Wang,Lulu Shen Key Laboratory of Developmental Genes and Human Disease in Ministry of Education,Department of Genetics and Developmental Biology,Southeast University Medical School,Nanjing 210009,China.
Objective To investigate the role of environmental factor—temperature in the regulation of aging process by unc-13 and sbt-1 in Caenorhabditis elegans. Methods The lifespan, the speed of pharynx pumping, and the intestinal autofluorescence of unc-13 and sbt-1 mutants were examined at different temperature conditions. In addition, to exclude the possible influences from other factors in unc-13 and sbt-1 mutants, the dauer formation, the thermotaxis, the brood size and the population percentage of the mutants expressing hsp16.2-gfp were further investigated. Results Mutations of unc-13 and sbt-1 significantly increased the mean and the maximum lifespans of nematodes cultured at 20 oC and 25 oC, while no noticeable increase was found at 15 oC in either the mean or the maximum lifespan. Investigations on the speed of pharynx pumping and the intestinal autofluorescence suggested that at 20 oC and 25 oC, mutations of unc-13 and sbt-1 could slow the aging process and delay the accumulation of aging-related cellular damage. Meanwhile, mutations of unc-13 or sbt-1 did not affect the dauer formation or the thermotaxis to different temperatures in nematodes. In contrast, at 20 oC and 25 oC conditions, mutations of unc-13 and sbt-1 significantly decreased the brood size and the percentage of nematodes expressing hsp16.2-gfp, while no such differences were detected at 15 oC. Moreover, the thermotolerance of unc-13 and sbt-1 mutants could be greatly strengthened after the 16-h heat shock at 35 oC. Conclusion The regulation of aging by unc-13 and sbt-1 is temperature-dependent. And the alterations in reproduction capability and stress response may be associated with the formation of this temperature-dependent property.
