A hyperpolarizing neuron recruits undocked innexin hemichannels to transmit neural information in Caenorhabditis elegans.

While depolarization of the neuronal membrane is known to evoke the neurotransmitter release from synaptic vesicles, hyperpolarization is regarded as a resting state of chemical neurotransmission. Here, we report that hyperpolarizing neurons can actively signal neural information by employing undocked hemichannels. We show that UNC-7, a member of the innexin family in Caenorhabditis elegans, functions as a hemichannel in thermosensory neurons and transmits temperature information from the thermosensory neurons to their postsynaptic interneurons. By monitoring neural activities in freely behaving animals, we find that hyperpolarizing thermosensory neurons inhibit the activity of the interneurons and that UNC-7 hemichannels regulate this process. UNC-7 is required to control thermotaxis behavior and functions independently of synaptic vesicle exocytosis. Our findings suggest that innexin hemichannels mediate neurotransmission from hyperpolarizing neurons in a manner that is distinct from the synaptic transmission, expanding the way of neural circuitry operations.

Toxicological effects of Tris (1,3-dichloro-2-propyl) phosphate exposure in adult male rats differ depending on the history of exposure in the neonatal period.

There is increasing concern about multiple high concentration exposure to toxins in disaster and emergency situations. However, conventional toxicology testing methods may not adequately address these situations. Thus, we assessed whether the toxic effects of exposure in the adulthood differ depending on the presence or absence of neonatal exposure to Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in male rats to investigate the effects of exposure history of chemicals. In the neonatal stage [postnatal days (PNDs) 1-7], animals were treated with either sesame oil (5 ml/kg/day) as a control or TDCIPP (250 mg/kg/day) dissolved in sesame oil. In adulthood (PND 101-107), animals were treated with either sesame oil (5 ml/kg/day) or TDCIPP (650 mg/kg/day). One day after the final administration, dissection was performed, and body and organ weight, hematology, blood biochemistry, and histopathology were examined. The results demonstrated that the toxic effects of TDCIPP exposure in adulthood on adrenal gland size, serum iron content, and unsaturated iron binding capacity were enhanced by TDCIPP exposure in the neonatal stage. From these findings, it was indicated that the toxic effects of TDCIPP exposure in the adult stage are affected by pediatric exposure. These results suggest that the toxic effects of high-dose and long-term unsteady exposure to chemicals in large-scale disasters may change based on the exposure history of chemicals.

Novel toxicity of tris(1,3-dichloro-2-propyl) phosphate in adult male rats.

The widespread use of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) as a flame retardant has led to its release to the environment. Thus, the toxicological effects of TDCIPP on humans and animals are of importance. For better understanding of its potential toxicities, TDCIPP (250, 500, or 650 mg/kg/day) or vehicle control was administrated orally to adult male Wistar-Imamichi rats for 7 days. After the final administration of compounds, organ weights, histopathology, blood biochemistry, and hematology were examined. Hepatic toxicity was observed at doses ≥ 500 mg/kg/day of TDCIPP, and renal toxicity was observed at 650 mg/kg/day. The anti-androgenic activity of TDCIPP was previously confirmed in vitro and in vivo, but weights of epididymis, an androgen-dependent organ, were not affected by TDCIPP treatment in adults. Serum alkaline phosphatase activity was significantly decreased in all TDCIPP-treated rats independent of dose. Hemoglobin concentration, hematocrit, red blood cell count, and reticulocyte count were decreased in all TDCIPP-treated rats, but mean corpuscular volume, total iron-binding capacity, and serum iron were normal, suggesting that renal anemia was caused by TDCIPP. Together with previous reports on effects of anti-androgenic substances on red blood cell indices, anemia caused by TDCIPP could be due to its anti-androgenic activity. These considerations will contribute to further assessment of the toxicity of the compound.

The effects of 28-day early-life exposure to triphenyl phosphate (TPhP) on odor preference and sexual behavior in female rats.

Many chemical substances are detectable in house dust, and they are consequently taken into our bodies via the mouth and nose. Triphenyl phosphate (TPhP), a flame retardant that has an estrogen-like effect in vitro, is present in house dust at high concentrations. Estrogen exposure during development has significant influences on reproductive behavior in rodents, and its effects persist until maturity. In the present study, we investigated the effect of early life exposure to TPhP on the reproductive behavior of female rats. Oral treatment with TPhP (25 or 250 mg/kg), ethinyl estradiol (EE; 15 µg/kg) as a positive control, or sesame oil as a negative control, were given to female rats (from birth to 28 days of age). The 8-week-old rats were bilaterally ovariectomized. At 12-15 weeks of age, the rats were subjected to odor preference and sexual behavior tests. In the odor preference test, the oil group showed significantly higher preference for male odor than female odor, but the low-dose TPhP treatment group lost the preference for male odor, indicating a possible outcome of early life TPhP exposure on sexual recognition. In the sexual behavior test, both the EE and TPhP treatment groups displayed significantly less proceptive behavior. These results suggest that early life exposure to TPhP disturbs the normal sexual behavior of female rats.

Genetic screens identified dual roles of microtubule-associated serine threonine kinase and CREB within a single thermosensory neuron in the regulation of Caenorhabditis elegans thermotaxis behavior.

Animals integrate sensory stimuli presented at the past and present, assess the changes in their surroundings and navigate themselves toward preferred environment. Identifying the neural mechanisms of such sensory integration is pivotal to understand how the nervous system generates perception and behavior. Previous studies on thermotaxis behavior of Caenorhabditis elegans suggested that a single thermosensory neuron AFD plays an important role in integrating the past and present temperature information and is essential for the neural computation that drives the animal toward the preferred temperature region. However, the molecular mechanisms by which AFD executes this neural function remained elusive. Here we report multiple forward genetic screens to identify genes required for thermotaxis. We reveal that kin-4, which encodes the C. elegans homolog of microtubule-associated serine threonine kinase, plays dual roles in thermotaxis and can promote both cryophilic and thermophilic drives. We also uncover that a thermophilic defect of mutants for mec-2, which encodes a C. elegans homolog of stomatin, can be suppressed by a loss-of-function mutation in the gene crh-1, encoding a C. elegans homolog CREB transcription factor. Expression of crh-1 in AFD restored the crh-1-dependent suppression of the mec-2 thermotaxis phenotype, indicating that crh-1 can function in AFD to regulate thermotaxis. Calcium imaging analysis from freely moving animals suggest that mec-2 and crh-1 regulate the neuronal activity of the AIY interneuron, a postsynaptic partner of the AFD neuron. Our results suggest that a stomatin family protein can control the dynamics of neural circuitry through the CREB-dependent transcriptional regulation within a sensory neuron.

Effect of downhill walking on next-day muscle damage and glucose metabolism in healthy young subjects.

This study aimed to investigate the effect of downhill walking on muscle damage and glucose metabolism in healthy subjects. All ten healthy young men and women (age, 24.0 ± 1.4 years) performed rest, uphill walking, and downhill walking trials. In the exercise trials, uphill (+ 5%) or downhill (- 5%) treadmill walking was performed at 6 km/h for 30 min. On the next day, muscle soreness was significantly higher in the downhill trial than in the uphill trial (P < 0.01). Respiratory metabolic performance did not differ between trials. However, carbohydrate oxidation was negatively correlated with plasma creatine kinase (r = - 0.41) and muscle soreness (r = - 0.47). Fasting blood glucose was significantly lower in the uphill trial than in the rest trial (P < 0.01) but not in the downhill trial. These observations suggest that downhill but not uphill walking causes mild delayed-onset muscle damage, which did not cause marked impairment in glucose metabolism. However, higher muscle damage responders might exhibit lower glucose metabolism.

Male Hatano low-avoidance rats show more active sexual behavior with lower plasma testosterone than high-avoidance rats.

Two inbred strains of Sprague-Dawley rats, known as the Hatano high- and low-avoidance animals (HAA and LAA respectively), have been selectively bred for high versus low rates of avoidance responses in a shuttle-box avoidance task. To investigate differences in the sexual behavior of Hatano rats, male HAA, LAA and SD rats were tested from 12 to 15 weeks of age. LAA rats exhibited more rapid and frequent sexual behavior than HAA or SD rats, and such differences increased with repeated sexual experience. Plasma testosterone levels tended to be lower in LAA rats than in HAA or SD rats, suggesting that active sexual behavior in LAA rats is not related to these levels. Strain differences in mating behavior between HAA and LAA rats may be caused by emotional responses to novelty.

Erratum to: The effect of Katsura-uri (Japanese pickling melon, Cucumis melo var. conomon) and its derived ingredient methylthioacetic acid on energy metabolism during aerobic exercise.

[This corrects the article DOI: 10.1186/s40064-015-1144-y.].

The effect of Katsura-uri (Japanese pickling melon, Cucumis melo var. conomon) and its derived ingredient methylthioacetic acid on energy metabolism during aerobic exercise.

PURPOSE: We investigated the effect of Katsura-uri (Japanese pickling melon; Cucumis melo var. conomon) on energy metabolism during exercise in human and animal studies. METHODS: Eight healthy men (mean age, 21.4 ± 0.7 years) participated in a single-blind, crossover study. Thirty minutes after ingesting the Katsura-uri drink or placebo drink, they exercised on a cycle ergometer at 40% maximal heart rate for 30 min. Respiratory gas analysis was performed during exercise to examine oxygen consumption and substrate utilization. Blood biochemical parameters were evaluated during exercise. In the animal study, the effect of methylthioacetic acid (MTA), a Katsura-uri derived component was examined in mice. Immediately after running at 25 m/min for 30 min, biochemical parameters in the hind limb muscle and blood of mice were measured. RESULTS: Oxygen consumption during exercise was higher in the Katsura-uri condition (19.8 ± 3.5 mL/kg/min) than the placebo condition (18.6 ± 3.0 mL/kg/min) (P < 0.05). The elevation of blood lactate was lower in the Katsura-uri condition (1.7 ± 0.4 mM) than the placebo condition (2.2 ± 0.6 mM) 15 min after beginning exercise (P < 0.05). There was a higher positive correlation between lactate concentration and carbohydrate oxidation during exercise in the Katsura-uri condition (R(2) = 0.86) compared to the placebo condition (R(2) = 0.47). The decrease in intermuscular pH and the increase in blood lactate following exercise were prevented by MTA supplementation (250 ppm) with significant differences in the MTA-supplemented group compared to the control group. CONCLUSIONS: These results suggest that the ingestion of Katsura-uri and/or MTA improves glucose metabolism and acidification in skeletal muscles during exercise in human and animal studies.

Factors affecting phenolic acid liberation from rice grains in the sake brewing process.

Phenolic acid (ferulic and p-coumaric acid) liberation from rice grains was examined using rice samples containing phenolic acid at different levels, using two sake mash simulated digestion tests to elucidate influencing factors. Phenolic acid levels in a digest made from steamed rice using dialyzed rice koji enzymes were smaller than levels in a rice koji self-digest. Differences in phenolic acid levels among rice samples in the rice koji self-digest were larger than levels in a digest of steamed rice. In the rice koji self-digest, phenolic acid levels in the ingredient rice grains or in the formed digest related to feruloylesterase (FE) activity in the rice koji. Addition of exogenous FE to rice koji self-digestion increased phenolic acid levels, while addition of xylanase (Xyl) showed weak effects. A concerted effect of FE and Xyl was not clearly observed. Addition of ferulic acid to koji made from α-rice grains raised FE activity, but it did not increase the activity of other enzymes. A similar phenomenon was observed in an agar plate culture of koji mold. These results indicated that ferulic acid levels in ingredient rice grains correlate with FE activities of koji, as a resulut, they affect the phenolic acid levels in sake mash.