Matsumoto M et al. (2005) Cell Metab "All roads lead to FoxO."

Accili D, Matsumoto M

[Cell Metab, 2005]

Stress-activated kinases control metabolism by antagonizing the early steps of insulin signal transduction. Two papers now demonstrate that Jnk, the prototypical stress-activated kinase, controls life span in Drosophila and C. elegans by promoting phosphorylation of the forkhead protein FoxO (Oh et al., 2005; Wang et al., 2005). The findings provide yet another mechanism by which metabolic and stress responses are integrated via phosphorylation of FoxO proteins.

Matsumoto, Shinya et al. (2015) International Worm Meeting "Analysis of intergenerational effects of starvation."

Matsumura, Yasuki, Matsumoto, Shinya, Morishita, Mayu, Sei, Megumi, Ogai, Midori, Kato, Kosuke, Saito, Haruka, Nishida, Ayano, Sawanaga, Akari, Okada, Sawako, Sakagami, Midori

[International Worm Meeting, 2015]

According to the DOHaD (Developmental Origins of Health and Disease) concept, poor nutritional environment during early life (including conception, embryogenesis, infancy and early childhood) induces changes in development that increase the disease risk in adult stage. The DOHaD is attracting many attention because not only it could change our view toward health and diseases, but also it causes concern about the health of our future generation. Generally, the three molecular events, DNA methylation, histone modifications, and non-coding RNAs are considered to be involved in DOHaD process in vertebrates, but the precise mechanism is not well defined. To gain information concerning the molecular mechanism of DOHaD, starvation was introduced to the parent worms, and the offsprings were analyzed for their fecundity, life span, mobility and fat accumulation. There were no difference observed in fecundity, life span and mobility between the offsprings derived from starvation-experienced and fed-parent worms. However, Nile Red staining showed that fat content was significantly increased in the offsprings derived from starvation-experienced worms compared with that of control offsprings. Fat accumulation was further indicated by gas chromatography analysis. DNA microarray is now being conducted to analyse the gene expression pattern.The data is in line with DOHaD concept, which may indicate that C.elegans can be used in DOHaD model animal.

Shinya Matsumoto et al. (2003) International Worm Meeting "Effect of endocrine disrupters on reproduction of C. elegans."

Yasuki Matsumura, Tohomiko Mori, Shinya Matsumoto

[International Worm Meeting, 2003]

Certain chemical compounds in the environments are reported to mimic the functions of endocrine hormones of many organisms and because of their potential function to disrupt the hormone balance in organisms, they are often termed endocrine disrupters. Some phthalates used as plastic softeners (such as butylbenzylphthalate and dibutylphthalate), alkylphenols used in polymers (such as nonylphenol, p-octylphenol, Bisphenol A), synthetic sex hormones (such as diethylstilbestrol(DES) and ethynylestradiol) and heavy metal-containing compounds (such as tributyltin) are among those suspected to be endocrine disrupters. Among those which are reported to be the effect of endocrine disrupters, its influence on sperm formation and/or production in mammals has been attracting the attention. While the production of oocytes in C.elegans hermaphrodite continues throughout its adulthood, that of sperm takes place only during the L4 stage and the number of produced sperm is fairly constant (about 300 sperms), which means the number of the progeny of a self-mating hermaphrodite is limited by the number of the sperms produced. Therefore, the potential effect of endocrine disrupters on the sperm formation could be assessed by counting the number of progeny of a hermaphrodite. We investigated the effect of these compounds on the reproduction properties of C.elegans using this methods. Two mixture was prepared; DES, Bisphenol A, nonylphenol, octylphenol, dibutyl phthalate, butylbenzyl phthalate and styrene monomer as A group and B group for the mixture of heavy metals containing Cu, Ni, Co, Mn, Zn, Pb and Sn. These mixture were added separately or together at various concentration to NGM plate and the number of progeny from a hermaphrodite raised on it was counted. When worms were raised on the plate containing A group or B group or A+B group, significant decrease in the number of progeny was not observed at any concentration. On the other hand, when they are raised on a plate containing both group at very low concentration (1-10 ppt), the number of progeny appeared to decrease to 60-70 % of that of control. We are seeking which of the components in the mixture is responsible for the effect together.

Matsumoto, Shinya et al. (2013) International Worm Meeting "Effect of Repeated Starvation on Fat Content in C.elegans."

Sawanaga, Akari, Sato, Nao, Kato, Kosuke, Yamamoto, Yukari, Matsumura, Yasuki, Matsumoto, Shinya

[International Worm Meeting, 2013]

It is widely considered that regular feeding rhythm is important to maintain our health in good condition. However, irregularity in feeding rhythm such as late supper and skipping meals can often occur due to busy modern life. If and how such irregular feeding pattern can affect our life is not always clear. The aim of this study is to evaluate the effect of irregular feeding rhythm on the various physiological aspects using C.elegans as model organism. Feeding patterns of human and worm are different; while human eat intermittently, worms eat continuously. Therefore, repeated starvation was introduced as the model of irregular feeding rhythm, because the regimen disturbs normal feeding pattern of worm. The cycle of 6 h starvation - 18 h feeding was introduced twice in adult worms, and its effect on fecundity, life span, mobility and fat accumulation was evaluated. No obvious effect was observed on fecundity, life span and mobility. However, fat content, assessed by Nile Red staining, in worm which experienced repeated starvation was shown to increase compared to that of worms which did not experience starvation. To further support the result, the expression of genes involved in fat metabolism such as fatty acid synthase (fasn-1), acetyl-CoA carboxylase (pod-2), O-acyl transferase (mboa-2) and worm sterol regulatory element binding protein (SREBP-1) ortholog (sbp-1) is currently under investigation by RT-PCR. The increment of fat in starvation-experienced worms may have resulted by the fat metabolic shift toward accumulation rather than consumption to prepare the food shortage.

Matsumoto, A. et al. (2019) International Worm Meeting "Integration of detected salt concentrations with motor state mediated by a single interneuron in C.elegans."

Matsumoto, A., Toyoshima, Y., Iino, Y.

[International Worm Meeting, 2019]

Animals navigate toward their preferred environment by integrating sensory inputs and their internal state. C. elegans migrates toward NaCl concentrations at which it was cultivated in the presence of food. C. elegans employs several strategies of NaCl chemotaxis, one of which is klinotaxis. Previous studies revealed several neurons that are required for klinotaxis; ASER, AIZ and SMB. However, how the information regarding NaCl concentration flows from sensory neurons to motor neurons remains unknown. Here we seek to find how NaCl information is conveyed from ASER through AIZ to SMB by calcium imaging. We found that ASER and AIZ respond to NaCl concentration changes in accordance with the frequency of head undulation, while SMB did not seem to respond directly to NaCl. We also found that the amplitude of calcium response of AIZ to NaCl concentration change is higher after cultivation at high NaCl concentration compared to the response after cultivation at low NaCl concentration. The amplitude of AIZ calcium response to NaCl concentration change also depended on basal level of AIZ activity. We then analyzed AIZ activity as well as the worm's movement and found AIZ activity correlates with forward and backward movement inside the olfactory chip, in that silencing AIZ activity roughly coincides with forward movement. These results suggest that AIZ integrates NaCl information with motor information.

Matsumoto H et al. (1991) Worm Breeder's Gazette "Complete sequence of tropomyosin gene, tmy-1, LGV of Caenorhabditis"

Kagawa H, Sugimoto K, Matsumoto H, Sakube Y

[Worm Breeder's Gazette, 1991]

Tropomyosin is a thin filament component of muscle structure. We cloned and sequenced genomic DNA and three species of cDNA. Tmy-1 gene encoded 16 exons and was expanding more than 12kb. All of this sequence located between cosmid clones F39B2 and K05C4 (just left of unc-54 I, no overlap cosmid and phage clones). The tmy-1 gene alternatively spliced into 3 isoforms. Two muscle and one cytoplasmic types were similar splicing patterns to that of other animals ( Drosophila TmII gene and chicken tropomyosin gene). The part of exon1 and exon2 was matched to the result of PCR experiment (Larry Schiliefer and Bob Waterston, personal communication). Two muscle types had identical amino acid sequences except 27 amino acid residues of C-terminal end. There was a typical promoter like sequence in 5' non-coding region of two muscle types (Fig.1). 5' end of the last cDNA was still missing. The same poly A signal was used in three isoforms, although there were other poly A signals in the 3' downstream of the gene. Tmy-1 gene expression of transcription factor control and splicing mechanism of tissue specific isoform are interested. [See Figure 1]

Shinya Matsumoto et al. (2004) East Asia Worm Meeting "Effect of oxidized fatty acids on viability of C.elegans."

Akiko Souma, Rie Kimura, Yasuki Matsumura, Tomohiko Mori, Tomoko Aso, Shinya Matsumoto

[East Asia Worm Meeting, 2004]

Oxidized fatty acids, when orally administered, cause toxic effect to organism, in the worst case, to the death. Although the adverse effect of oxidative stress upon cell or cellular components, such as plasma membrane, protein and DNA, has been intensively studied, the exact molecular mechanism concerning toxic effect of oral administration of oxidized fatty acids is not fully understood. To evaluate the effect of oxidized fatty acids from the stand point of nutrition and bio-safety, we fed C.elegans with oxidized fatty acids and observed the effect of the oxidized fatty acids upon fertility, life span and the expression of genes which are implicated on antioxidative stress.Oxidized oleic (18:1), linoleic (18:2), arachidonic (20:4), icosapentaenoic (20:5) and docosahexaenoic acid (22:6) were incorporated into debris of OP50 membrane and seeded with live OP50 on NGM plate. N2 eggs were laid on the plate and the hatched worms were exposed to the oxidized fatty acids throughout their life-time. The number of progeny derived from the oxidized fatty acids-fed worms showed little change compared to those of normal OP50-fed worms, indicating oxidized fatty acids had no effect of the fertility of worms. Oxidized fatty acids induced increased death around 7-10 days after hatch, which was not observed in OP50-fed worms. The average life span (50% death length) and the maximum life span were less influenced by the oxidized fatty acids. This indicates that oxidized fatty acid susceptibility increased temporarily or stage-specifically during worm life time. The expression of SOD and catalase have shown to be enhanced during this stage.

Matsumoto, Shinya et al. (2017) International Worm Meeting "Repeated starvation leads to fat accumulation in C.elegans."

Sawanaga, Akari, Yamamoto, Kanae, Nagao, Misaki, Matsumoto, Shinya, Yamamoto, Sayuri, Yamamoto, Rena, Sato, Nao

[International Worm Meeting, 2017]

Our aim is to define how repeated starvation affects the biology, physiology and molecular biology of organism, by using C.elegans. Adult worms were exposed to two cycles of 6hr starvation-18hr feeding diet pattern, and their fat accumulation was analyzed by Nile Red staining and biochemical quantification. The expression of genes involved in fat synthesis (pod-2, fasn-1, mboa-2, sbp-1) and fat degradation (hosl-1, lipl-4, cpt-1, cpt-2, B03003.3, F53a2.7) in the worms were also determined by real-time RT-PCR. Both fluorescent analysis and biochemical quantification showed that fat content of worms experienced repeated starvation increased. There was no obvious change in the expression of genes involved in fat synthesis, but those of fat degradation tended to decrease, which is consistent with the increment of fat in worms experienced repeated starvation. The life span, fecundity and mobility of worms experienced repeated starvation did not show differences compared to those of the control worms. Our results indicate that repeated starvation causes metabolic and nutritional effect on organism. It is often mentioned that repeated, and often unsuccessful, dieting leads to weight regaining of all or more than initial loss, which is referred as rebound weight gain. However, it is difficult to know whether such weight gain is caused by metabolic and/or genetic alteration. Our data in worms may provide a molecular basis of rebound weight gain.

Shinya Matsumoto et al. (2005) International Worm Meeting "Effect of oxidized fatty acids on C. elegans redox status."

Tomoko Aso, Rie Kimura, Shinya Matsumoto, Tomohiko Mori, Akiko Soma, Yasuki Matsumura

[International Worm Meeting, 2005]

Oxidized fatty acids, when orally administered, cause toxic effect to organism. Although the adverse effect of oxidative stress upon cell and cellular components such as plasma membrane, protein and DNA, has been intensively studied, the exact molecular mechanism concerning toxic effect of oral administration of oxidized fatty acids is not fully understood. To evaluate the effect of oxidized fatty acids from the stand point of nutrition and bio-safety, we fed C.elegans with oxidized fatty acids and observed the effect of the oxidized fatty acids upon fertility, life span and the expression of genes which are implicated on antioxidative stress. Oxidized oleic (18:1), linoleic (18:2), arachidonic (20:4), icosapentaenoic (20:5) and docosahexaenoic acid (22:6) were incorporated into debris of OP50 membrane and seeded with live OP50 on NGM plate. N2 eggs were laid on the plate and the hatched worms were exposed to the oxidized fatty acids throughout their development. The number of progeny derived from the oxidized fatty acids-fed worms showed little change compared with that of normal OP50-fed worms, indicating oxidized fatty acids had no effect of the fertility of worms. Oxidized fatty acids induced increased death around 7-10 days after hatch, which was not observed in OP50-fed worms. The average life span (50% death length) and the maximum life span were less influenced by the oxidized fatty acids. This indicates that oxidized fatty acid susceptibility increased temporarily or stage-specifically during worm life time. The expression of SOD and catalase have shown to be enhanced during this stage. We then asked whether the fed oxidized fatty acid have changed redox status in C. elegans by electron spin resonance (ESR). ESR detect free radical compound based on the existence of unpaired electron in the molecule and gives specific spectrum of the radical. When stable nitroxide radicals such as Tempol are administered to an animal, they are reduced either by hosts' redox systems or endogenous free radicals and consequently the Tempol signal intensity is weakened. Therefore, by comparing the decrease rate of Tempol signal intensity, the endogenous redox status of the animal can be evaluated. We fed N2 worms with hydroperoxides and the oxidized fatty acids. Tempol was added to the worms and the effects of the oxidants on redox status of the worms was examined by ESR. In worms which were fed bacteria together with oxidized fatty acids and hydroperoxides, enhanced reduction activity of Tempol had been observed in comparison with worms fed without oxidants. These results may indicate the oxidized fatty acids may induce oxidative stress on worm by increasing the endogenous free radicals.

Matsumoto A et al. (2024) Proc Natl Acad Sci U S A "Neuronal sensorimotor integration guiding salt concentration navigation in Caenorhabditis elegans."

Goda K, Matsumoto A, Isozaki A, Toyoshima Y, Iino Y, Zhang C

[Proc Natl Acad Sci U S A, 2024]

Animals navigate their environment by manipulating their movements and adjusting their trajectory which requires a sophisticated integration of sensory data with their current motor status. Here, we utilize the nematode <i>Caenorhabditis elegans</i> to explore the neural mechanisms of processing the sensory and motor information for navigation. We developed a microfluidic device which allows animals to freely move their heads while receiving temporal NaCl stimuli. We found that <i>C. elegans</i> regulates neck bending direction in response to temporal NaCl concentration changes in a way which is consistent with a <i>C. elegans</i>' navigational strategy which regulates traveling direction toward preferred NaCl concentrations. Our analysis also revealed that the activity of a neck motor neuron is significantly correlated with neck bending and activated by the decrease in NaCl concentration in a phase-dependent manner. By combining the analysis of behavioral and neural response to NaCl stimuli and optogenetic perturbation experiments, we revealed that NaCl decrease during ventral bending activates the neck motor neuron which counteracts ipsilateral bending. Simulations further suggest that this phase-dependent response of neck motor neurons can facilitate curving toward preferred salt concentrations.