Inhibition of Citric Acid-Induced Dentin Erosion by an Acidulated Phosphate Sodium Monofluorophosphate Solution.

Sodium monofluorophosphate (Na2FPO3, MFP) is mainly used as an ingredient in fluoride-based dentifrices as it has a high safety profile, with one-third of the toxicity of sodium fluoride (NaF), as well as the ability to reach deep into the dentin. The purpose of this study was to assess the prevention of dentin erosion by MFP upon exposure to citric acid, which has a chelating effect, and to compare the effects to those of the conventional acidulated phosphate fluoride (APF) application method. Bovine dentin was used, and four groups were created: (i) APF (9000 ppmF, pH 3.6) 4 min group; (ii) acidulated phosphate MFP (AP-MFP, 9000 ppmF, pH 3.6) 4 min group; (iii) AP-MFP 2 min + APF 2 min (dual) group; and (iv) no fluoride application (control) group. Compared with the conventional APF application method, the application of AP-MFP was shown to significantly reduce substantial defects, mineral loss, and lesion depth; better maintain Vickers hardness; and promote the homogenous aggregation of fine CaF2 particles to seal the dentin tubules, enhancing acid resistance in their vicinity. The ΔZ value of the AP-MFP group was 2679 ± 290.2 vol% µm, significantly smaller than the APF group's 3806 ± 257.5 vol% µm (p < 0.01). Thus, AP-MFP-based fluoride application could effectively suppress citric acid-induced demineralization and could become a new, more powerful, and biologically safer professional-care method for preventing acid-induced dentin erosion than the conventional method.

The effect of mask fit test on the association between the concentration of metals in biological samples and the results of time-weighted average personal exposure: A study on Japanese male welders.

OBJECTIVES: The mask fit test confirms whether the wearing condition of the wearer's face and the facepiece of the respirators are used appropriately. This study aimed to examine whether the results of the mask fit test affect the association between the concentration of metals related to welding fumes in biological samples and the results of time-weighted average (TWA) personal exposures. METHODS: A total of 94 male welders were recruited. Blood and urine samples were obtained from all participants to measure the metal exposure levels. Using personal exposure measurements, the 8-h TWA (8 h-TWA) of respirable dust, TWA of respirable Mn, and 8-h TWA of respirable Mn were calculated. The mask fit test was performed using the quantitative method specified in the Japanese Industrial Standard T8150:2021. RESULTS: Fifty-four participants (57%) passed the mask fit test. Only in the Fail group of the mask fit test, it was observed that blood Mn concentrations be positively associated with the results of TWA personal exposure after adjusting for multivariate factors (8-h TWA of respirable dust; coefficient, 0.066; standard error (SE), 0.028; P = 0.018, TWA of respirable Mn: coefficient, 0.048; SE, 0.020; P = 0.019, 8 h-TWA of respirable Mn: coefficient, 0.041; SE, 0.020; P = 0.041). CONCLUSIONS: The results clarify that welders with high concentrations of welding fumes in their breathing air zone are exposed to dust and Mn if there is leaking air owing to the lack of fitness between respirators and the wearer's face when using human samples in Japan.

Associations between welding fume exposure and neurological function in Japanese male welders and non-welders.

OBJECTIVES: There are some studies reporting the association between (manganese [Mn]) exposure to welding fume and neurological dysfunction. This study examined the relationship between Mn exposure and neurological behavior in Japanese male welders and non-welders using biological samples, which to date has not been assessed in Japan. METHODS: A total of 94 male welders and 95 male non-welders who worked in the same factories were recruited. The blood and urine samples were obtained from all the participants to measure Mn exposure levels. Neurological function tests were also conducted with all participants. The sampling of the breathing air zone using a personal sampler was measured for welders only. RESULTS: The odds ratios (ORs) for the Working Memory Index (WMI) scores were significantly higher among all participants in the low blood Mn concentration group than those in the high blood Mn concentration group (OR, 2.77; 95% confidence interval [CI], 1.24, 6.19; P = .013). The association of WMI scores and blood Mn levels in welders had the highest OR (OR, 3.73; 95% CI, 1.04, 13.38; P = .043). Although not statistically significant, a mild relationship between WMI scores and blood Mn levels was observed in non-welders (OR, 2.09; 95% CI, 0.63, 6.94; P = .227). CONCLUSIONS: The results revealed a significant positive relationship between blood Mn and neurological dysfunction in welders. Furthermore, non-welders at the same factories may be secondarily exposed to welding fumes. Further research is needed to clarify this possibility.

Neurobehavioral effects of acute low-dose whole-body irradiation.

Radiation exposure has multiple effects on the brain, behavior and cognitive functions. It has been reported that high-dose (>20 Gy) radiation-induced behavior and cognitive aberration partly associated with severe tissue destruction. Low-dose (<3 Gy) exposure can occur in radiological disasters and cerebral endovascular treatment. However, only a few reports analyzed behavior and cognitive functions after low-dose irradiation. This study was undertaken to assess the relationship between brain neurochemistry and behavioral disruption in irradiated mice. The irradiated mice (0.5 Gy, 1 Gy and 3 Gy) were tested for alteration in their normal behavior over 10 days. A serotonin (5-HT), Dopamine, gamma-Aminobutyric acid (GABA) and cortisol analysis was carried out in blood, hippocampus, amygdala and whole brain tissue. There was a significant decline in the exploratory activity of mice exposed to 3 Gy and 1 Gy radiation in an open field test. We observed a significant short-term memory loss in 3 Gy and 1 Gy irradiated mice in Y-Maze. Mice exposed to 1 Gy and 3 Gy radiation exhibited increased anxiety in an elevated plus maze (EPM). The increased anxiety and memory loss patterns were also seen in 0.5 Gy irradiated mice, but the results were not statistically significant. In this study we observed that neurotransmitters are significantly altered after irradiation, but the neuronal cells in the hippocampus were not significantly affected. This study suggests that the low-dose radiation-induced cognitive impairment may be associated with the neurochemical in low-dose irradiation and unlike the high-dose scenario might not be directly related to the morphological changes in the brain.

Local Anesthetics Inhibit Transient Receptor Potential Vanilloid Subtype 3 Channel Function in Xenopus Oocytes.

BACKGROUND: The transient receptor potential vanilloid subtype 3 (TRPV3) channel is activated by innocuous temperature and several chemical stimuli. It is proposed to be involved in pathological pain development and is therefore considered a potential target for treating pain. Local anesthetics have been used for patients with both acute and chronic pain. Although blockage of the voltage-gated sodium channel is the primary mechanism by which local anesthetics exert their effects, they cannot be explained by this mechanism alone, especially in pathologic states such as chronic pain. Indeed, the effects of local anesthetics on multiple targets involved in the pain pathway have been reported. It has also been suggested that modulating the function of transient receptor potential (TRP) channels (eg, TRPV1 and transient receptor potential ankyrin 1 [TRPA1]) is one of the mechanisms of action of local anesthetics. However, the effects of local anesthetics on TRPV3 have not been reported. METHODS: We expressed TRPV3 in Xenopus oocytes and investigated the effects of local anesthetics on 2-aminoethoxydiphenyl borate (2APB)-induced currents using 2-electrode voltage-clamp techniques. RESULTS: Clinically used local anesthetics inhibited the 2APB-activated currents from the TRPV3 channel in a concentration-dependent manner at pharmacologically relevant concentrations with half maximal inhibitory concentration (IC50) values of 2.5 (lidocaine), 1.4 (mepivacaine), 0.28 (ropivacaine), and 0.17 (bupivacaine) mmol/L, respectively. Conversely, these local anesthetics also directly induced currents at higher concentrations, although these currents were quite small compared to the 2APB-induced currents. We found that the inhibition of TRPV3 by lidocaine is noncompetitive and independent of intracellular signaling cascades. 2APB-induced TRPV3 currents were reduced by extracellular N-(2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX-314) but not by intracellular QX-314 nor benzocaine. Moreover, lidocaine showed a use-dependent block in TRPV3 inhibition. Finally, QX-314 appeared to slightly permeate the activated TRPV3 channel pore based on examination of oocytes coexpressing TRPV3 and a sodium channel. These results suggest that local anesthetics could inhibit TRPV3 channel function by extracellular interactions of their charged forms with the channel pore. CONCLUSIONS: Local anesthetics inhibited TRPV3 2APB-induced currents at pharmacologically relevant concentrations when TRPV3 was expressed in Xenopus oocytes. These effects seem to occur via an extracellular interaction between the charged form of the anesthetic with the TRPV3 channel pore. These results help to elucidate the mechanisms of action of local anesthetics.

Changes over time in pulmonary inflammatory response in rat lungs after intratracheal instillation of nickel oxide nanoparticles.

OBJECTIVE: Nickel oxide nanoparticles (NiONPs) are representative metal oxide NPs and are categorized as an insoluble nickel compound. Our previous studies suggested that NiONPs have more pulmonary toxicity than micron-sized NiO because they may dissolve slowly and produce many more Ni ions. We confirmed the hypothesis that the slow dissolution of NiONPs induces a change in inflammatory response over time. METHOD: We reanalyzed our previous data on intratracheally instilled NiONP to rats and focused on Ni retention in the lungs and the lung weight ratio for each rat to the mean of control rat lungs. We also measured the solubility of NiONPs and micron-sized NiO samples by means of an artificial lysosomal fluid (ALF, pH 4.5). RESULTS: The in vivo test of instilled NiONPs resulted in the biomarkers reaching their peak values at 1 week or 1 month, and not at 3 days, after instillation. We found that as the NiO mass in the lung increased, the lung weight ratios tended to increase. The relationships shifted to more toxic at 3 days to 1 month (P < .01). Compared to the dissolution of NiONPs in the ALF that took roughly 1 week, the dissolution of NiONPs in vivo was take about 1 month or more. CONCLUSION: When intratracheally instilled NiONPs dissolve slowly in the phagolysosomes of alveolar macrophages (AM), the resulting Ni ions cause the AM to transform into foamy cells at 1 month, and the inflammatory response persists even at 3 months after instillation.

Exposure to 1-bromopropane vapors during pregnancy enhances the development of hippocampal neuronal excitability in rat pups during lactation.

OBJECTIVES: Although 1-Bromopropane (1-BP) exposure has been reported to cause neurotoxicity in adult humans and animals, its effects on the development of the central nervous system remain unclear. Recently, we reported delayed developmental neurotoxicity (DNT) upon 1-BP exposure in rats. Here we aimed to study the effect of prenatal 1-BP exposure on the hippocampal excitability in the juvenile offspring. METHODS: Pregnant Wistar rats were exposed to vaporized 1-BP for 20 days (6 h/d) with concentrations of 0 (control), 400, or 700 ppm. Hippocampal slices were prepared from male offspring during postnatal days (PNDs) 13, 14, and 15. Field excitatory postsynaptic potential (fEPSP) and population spike (PS) were recorded simultaneously from the CA1 region. RESULTS: In the exposed groups, the stimulation/response relationships of fEPSP slope and PS amplitude were enhanced more than in the control group at PND 14. Analysis of fEPSP-spike coupling demonstrated increased values of Top and Eslope50 in the exposed groups. Real-time PCR analysis showed a significant increase in the mRNA levels of the adult type Nav 1.1 Na+ channel subunit and the GluR1 glutamate receptor subunit in the hippocampus of the 700 ppm group at PND 14. CONCLUSIONS: Our results provide evidence that prenatal exposure to 1-BP accelerates developmental enhancement of hippocampal excitability in the pups before eye-opening. The current study suggests that our evaluation method of DNT is applicable to the industrial chemical 1-BP.

[Cardio-oncology - elucidation of the mechanism of cardiac dysfunction caused by cancer therapy and cancer cachexia].

Cardiovascular disorders in cancer patients with cachexia have recently become a great concern. However, the relationship between cancer cachexia and cardiac dysfunction remains unclear, due to lack of suitable models. We established a novel murine model of cancer cachexia by implantation of 85As2 cells, a cell line derived from human gastric cancer cells, presenting anorexia, weight loss and low fat-free mass similar to those observed in patients. Moreover, cardiac dysfunction is expected in this model, which has not been yet examined. In the present study, we firstly evaluated cardiac functions with the model. Secondly, we investigated effects of voluntary wheel running (VWR) on cachexia-induced cardiac dysfunction using this model, as the exercise is considered to be one of therapies for chronic heart failure. 85As2 cells were transplanted subcutaneously into mice, which observed a symptomatic cachexia; decrease in body, skeletal muscle weight, and food intake. In addition, this cachexia mouse developed severe cardiac atrophy and left ventricular ejection fraction (LVEF) also markedly reduced with cachexia progression. Moreover, VWR suppressed the decrease in food intake and skeletal muscle weight loss in this model, and improved LVEF with suppression of heart weight loss. These results imply that our 85As2-cachexia mice models show cardiac dysfunction and VWR may improve not only cachexia symptoms but also cardiac dysfunction. As exercise therapy is generally introduced for the purpose of improving heart failure symptoms, this study suggests a possible therapeutic effect of exercise on cardiac dysfunction induced by cancer cachexia.

Carvacrol inhibits the neuronal voltage-gated sodium channels Nav1.2, Nav1.6, Nav1.3, Nav1.7, and Nav1.8 expressed in Xenopus oocytes with different potencies.

Carvacrol is the predominant monoterpene in essential oils from many aromatic plants. Several animal studies showing analgesic effects of carvacrol indicate potential of carvacrol as a new medication for patients with refractory pain. Voltage-gated sodium channels (Nav) are thought to have crucial roles in the development of inflammatory and neuropathic pain, but there is limited information about whether the analgesic mechanism of carvacrol involves Nav. We used whole-cell, two-electrode, voltage-clamp techniques to examine the effects of carvacrol on sodium currents in Xenopus oocytes expressing α subunits of Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8. Carvacrol dose-dependently suppressed sodium currents at a holding potential that induced half-maximal current. The half-maximal inhibitory concentration values for Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 were 233, 526, 215, 367, and 824 µmol/L, respectively, indicating that carvacrol had more potent inhibitory effects towards Nav1.2 and Nav1.6 than Nav1.3, Nav1.7, and Nav1.8. Gating analysis showed a depolarizing shift of the activation curve and a hyperpolarizing shift of the inactivation curve in all five α subunits following carvacrol treatment. Furthermore, carvacrol exhibits a use-dependent block for all five α Nav subunits. These findings provide a better understanding of the mechanisms associated with the analgesic effect of carvacrol.

The effect of environmental factors in childcare facilities and individual lifestyle on obesity among Japanese preschool children; a multivariate multilevel analysis.

Lifestyle in preschool children is associated with the onset of childhood obesity. However, the effect of environmental factors in childcare facilities on lifestyle and obesity in preschool children is unknown. The aim of this study was to determine the effect of environmental factors in childcare facilities on the association between obesity and individual lifestyle in preschool children.Subjects included 2902 infants, aged 4 to 6 years old in Kitakyushu City, Japan. A stratified multilevel analysis was conducted with 2 strata: factors related to individual lifestyle and maternal factors as the individual level and factors related to the childcare facility as the environmental level. Two-level multilevel regression analysis was conducted with the presence or absence of obesity.The proportion of infants with obesity was 4.2%. The childhood obesity was significantly associated with the mastication, nutritional methods during infancy, absence of breakfast, presence of skipping meals due to overeating of snacks, usual play activity, screen time on weekdays, maternal body mass index, and maternal weight increase during pregnancy at the individual level. On the other hand, childhood obesity had a significantly negative association with the receiving snacks in facilities by using multilevel analysis.The present study revealed that establishing and maintaining environmental factors in childcare facilities may play important roles in the prevention of obesity from early childhood.

Cancer Risks of Hexavalent Chromium in the Respiratory Tract.

Hexavalent chromium (Cr(VI)) compounds are recognized as carcinogens in the respiratory tract, giving rise to cancers of the lung, nose and nasal sinuses, especially in certain occupational environments. Inhalation exposure of Cr(VI)-containing particles, dusts and fumes commonly occurs in chromium-related occupational environments, such as chromium production, plating, welding of chromium-containing metals and alloys, electroplating, chromium-containing pigments and paints. Epidemiological surveys of chromium compounds have shown strong associations between exposure to Cr(VI) and mortality due to lung cancer, as well as positive associations with cancers of the nose and nasal cavity. Nasal symptoms, such as nasal irritation, ulceration and perforation of the nasal septum, nasal turbinate engorgement and hypertrophy, are important signs for the early diagnosis of lung cancer and cancers of the nose and nasal cavity in those with an occupational history of Cr(VI) exposure. Cr(VI) exposure in the workplace remains a serious problem as a cause of lung cancer and cancers of nose and nasal cavity, especially in relatively small enterprises that use chromium compounds. Appropriate protection for workers should be considered in occupations that involve exposure to chromium compounds.

The neurosteroid allopregnanolone sulfate inhibits Nav1.3 α subunit-containing voltage-gated sodium channels, expressed in Xenopus oocytes.

The neurosteroid allopregnanolone has potent analgesic effects, and its potential use for neuropathic pain is supported by recent reports. However, the analgesic mechanisms are obscure. The voltage-gated sodium channels (Nav) α subunit Nav1.3 is thought to play an essential role in neuropathic pain. Here, we report the effects of allopregnanolone sulfate (APAS) on sodium currents (INa) in Xenopus oocytes expressing Nav1.3 with ß1 or ß3 subunits. APAS suppressed INa of Nav1.3 with ß1 and ß3 in a concentration-dependent manner (IC50 values; 75 and 26 µmol/L). These results suggest the possible importance of Nav1.3 inhibition for the analgesic mechanisms of allopregnanolone.

Prenatal exposure to valproic acid alters the development of excitability in the postnatal rat hippocampus.

Prenatal valproic acid (VPA) exposure is a well-known animal model of autism spectrum disorder (ASD) that produces alterations in embryonic and adult neurogenesis as well as adolescent/adulthood neurobehavioral phenotypes. However, the effects of prenatal VPA exposure on neural network excitability, especially during the synaptogenic period around eye opening, are not fully understood. In this study, we orally administered VPA (300 mg/kg) to pregnant Wistar rats on gestation day 15 and subsequently performed field potential recording in the CA1 area of hippocampal slices obtained from control (saline-exposed) and VPA-exposed rat pups between postnatal day (PND) 13 and PND18. In control slices, we observed an abrupt enhancement of stimulation-dependent responses including population spike (PS) amplitudes and field excitatory postsynaptic potential (fEPSP) slopes at PND16, which coincided with the average day of eye opening. In contrast, VPA-exposed pups exhibited delayed eye opening (PND17) and gradual rather than abrupt increases in PS amplitudes and fEPSP slopes over the duration of the synaptogenic period. We next investigated the involvement of ambient GABA (γ-aminobutyric acid) in PS generation using bicuculline methiodide (BMI), a GABA type A (GABAA) receptor antagonist. In control slices, BMI enhanced PS amplitudes during PND14-15 (before eye opening) and had little effect thereafter during PND16-17; a subsequent regression model analysis of BMI ratios (the ratio of PS amplitudes in the presence and absence of BMI) indicated a possible developmental change between these periods. In contrast, almost identical regression models were obtained for BMI ratios during PND14-15 and PND16-17 in the VPA-exposed group, indicating the absence of a developmental change. Our results suggest that prenatal VPA exposure accelerates the development of hippocampal excitability before eye opening. Moreover, our experimental model can be used as a novel approach for the evaluation of developmental neurotoxicity.

Prenatal exposure to 1-bromopropane causes delayed adverse effects on hippocampal neuronal excitability in the CA1 subfield of rat offspring.

OBJECTIVES: Neurotoxicity of 1-bromopropane (1-BP) has been reported in occupational exposure, but whether the chemical exerts developmental neurotoxicity is unknown. We studied the effects of prenatal 1-BP exposure on neuronal excitability in rat offspring. METHODS: We exposed dams to 1-BP (700 ppm, 6 h a day for 20 days) and examined hippocampal slices obtained from the male offspring at 2, 5, 8, and 13 weeks of age. We measured the stimulation/response (S/R) relationship and paired-pulse ratios (PPRs) of the population spike (PS) at the interpulse intervals (IPIs) of 5 and 10 ms in the CA1 subfield. RESULTS: Prenatal 1-BP exposure enhanced S/R relationships of PS at 2 weeks of age; however, the enhancement diminished at 5 weeks of age until it reached control levels. Prenatal 1-BP exposure decreased PPRs of PS at 2 weeks of age. After sexual maturation, however, the PPRs of PS increased at 5-ms IPI in rats aged 8 and 13 weeks. CONCLUSIONS: Our findings indicate that prenatal 1-BP exposure in dams can cause delayed adverse effects on excitability of pyramidal cells in the hippocampal CA1 subfield of offspring.

Antidepressants inhibit Nav1.3, Nav1.7, and Nav1.8 neuronal voltage-gated sodium channels more potently than Nav1.2 and Nav1.6 channels expressed in Xenopus oocytes.

Tricyclic antidepressants (TCAs) and duloxetine are used to treat neuropathic pain. However, the mechanisms underlying their analgesic effects remain unclear. Although many investigators have shown inhibitory effects of antidepressants on voltage-gated sodium channels (Nav) as a possible mechanism of analgesia, to our knowledge, no one has compared effects on the diverse variety of sodium channel α subunits. We investigated the effects of antidepressants on sodium currents in Xenopus oocytes expressing Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 with a ß1 subunit by using whole-cell, two-electrode, voltage clamp techniques. We also studied the role of the ß3 subunit on the effect of antidepressants on Nav1.3. All antidepressants inhibited sodium currents in an inactivated state induced by all five α subunits with ß1. The inhibitory effects were more potent for Nav1.3, Nav1.7, and Nav1.8, which are distributed in dorsal root ganglia, than Nav1.2 and Nav1.6, which are distributed primarily in the central nervous system. The effect of amitriptyline on Nav1.7 with ß1 was most potent with a half-maximal inhibitory concentration (IC50) 4.6 µmol/L. IC50 for amitriptyline on Nav1.3 coexpressed with ß1 was lowered from 8.4 to 4.5 µmol/L by coexpression with ß3. Antidepressants predominantly inhibited the sodium channels expressed in dorsal root ganglia, and amitriptyline has the most potent inhibitory effect. This is the first evidence, to our knowledge, showing the diverse effects of antidepressants on various α subunits. Moreover, the ß3 subunit appears important for inhibition of Nav1.3. These findings may aid better understanding of the mechanisms underlying the pain relieving effects of antidepressants.

A cross-fostering analysis of bromine ion concentration in rats that inhaled 1-bromopropane vapor.

OBJECTIVE: Inhaled 1-bromopropane decomposes easily and releases bromine ion. However, the kinetics and transfer of bromine ion into the next generation have not been clarified. In this work, the kinetics of bromine ion transfer to the next generation was investigated by using cross-fostering analysis and a one-compartment model. METHODS: Pregnant Wistar rats were exposed to 700 ppm of 1-bromopropane vapor for 6 h per day during gestation days (GDs) 1-20. After birth, cross-fostering was performed between mother exposure groups and mother control groups, and the pups were subdivided into the following four groups: exposure group, postnatal exposure group, gestation exposure group, and control group. Bromine ion concentrations in the brain were measured temporally. RESULTS: Bromine ion concentrations in mother rats were lower than those in virgin rats, and the concentrations in fetuses were higher than those in mothers on GD20. In the postnatal period, the concentrations in the gestation exposure group decreased with time, and the biological half-life was 3.1 days. Conversely, bromine ion concentration in the postnatal exposure group increased until postnatal day 4 and then decreased. This tendency was also observed in the exposure group. A one-compartment model was applied to analyze the behavior of bromine ion concentration in the brain. By taking into account the increase of body weight and change in the bromine ion uptake rate in pups, the bromine ion concentrations in the brains of the rats could be estimated with acceptable precision.

Prenatal Exposure to 1-Bromopropane Suppresses Kainate-Induced Wet Dog Shakes in Immature Rats.

1-Bromopropane (1-BP) is used in degreasing solvents and spray adhesives. The adverse effects of 1-BP have been reported in human cases and adult animal models, and its developmental toxicity has also been reported, but its effects on developmental neurotoxicity have not been investigated in detail. We evaluated the effects in rat pups of prenatal exposure to 1-BP on behaviors such as scratching and wet dog shakes (WDS), which were induced by injection of kainate (KA). Pregnant Wistar rats were exposed to vaporized 1-BP with 700 ppm from gestation day 1 to day 20 (6 h/day). KA at doses of 0.1, 0.5, and 2.0 mg/kg were intraperitoneally injected into a control group and a 1-BP-exposed group of pups on postnatal day 14. There was no significant difference in scratching between the control and the prenatally 1-BP-exposed groups, while suppression of the occurrence ratio of WDS was observed at the low dose of 0.1 mg/kg of KA in the prenatally 1-BP-exposed pups. Our results suggest that prenatal exposure to 1-BP affects neurobehavioral responses in the juvenile period.