Effect of maternal exposure to Curcumae Rhizoma during pregnancy on neurodevelopment and apoptosis mechanism in offspring / 中国中药杂志

Curcumae Rhizoma is a Chinese medicinal herb that is contraindicated during pregnancy. Cold-congelation and blood-stasis are corresponding syndromes to Curcumae Rhizoma. Whether syndrome-based treatment is associated with developmental neurotoxicity of Curcumae Rhizoma remains to be unclear. To verify the theory of traditional Chinese medicine of "syndrome-based treatment during pregnancy", the present study induced the mice blood stasis model by immersing mice in ice water. Pregnant C57 BL/6 wild type(WT) mice and pregnant Nrf2 knock out(KO) mice were randomly divided into control groups and Rhizoma Curcumae exposure groups. The mice were exposed to Rhizoma Curcumae during day 5 to day 18 after pregnancy. The neurodevelopment was examined to evaluate the differences of developmental neurotoxicity between normal and blood-stasis pregnant mice exposed to Rhizoma Curcumae. caspase-3 and caspase-9 activity in brain of the offspring were measured by colorimetric assays. Bcl-2 mRNA and protein expression in brain of the offspring were examined by Real-time RT-PCR and Western blot, respectively. According to the findings, C57 BL/6 mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) had a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring, compared with the normal control group, but with no significant change in those of blood-stasis pregnant mice offspring. However, mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) showed no change in Bcl-2 gene expression and p38 MAPK phosphorylation in brain of the offspring. Nrf2 gene knockout using CRISPR/Cas9 resulted in a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring. In conclusion, developmental neurotoxicity of the blood-stasis pregnant mice exposed to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Nrf2 activation involved in the phenomenon of Rhizoma Curcumae of "syndrome-based treatment during pregnancy", but the upstream signal pathway mechanism value shall be further investigated.

Influence of aluminum chloride exposure on embryonic development of zebrafish and neurobehavior of juvenile fish / 中华劳动卫生职业病杂志

Objective@#To investigate the influence of aluminum chloride (AlCl3) solution on the embryon-ic development of zebrafish and neurobehavior of juvenile fish.@*Methods@#The embryos of zebrafishat 6 hours after fertilization were exposed to AlCl3 solution at a concentration of 0, 55.0, 60.5, 66.6, 73.5, 80.5, or 100.0 mg/L, and embryonic hatching rates at 48 and 72 hours after fertilization were calculated. The embryos of zebrafishat 6 hours after fertilization were exposed to AlCl3 solution at a concentration of 0, 60.0, 72.0, 86.4, 103.7, or 124.4 mg/L, and the embryonic mortality rates at 12, 24, 48, 72, and 96 hours after fertilization were calculat-ed. The embryos of zebrafish at 6 hours after fertilization were exposed to AlCl3 solution at a concentration of 0, 50, 100, 200, 400, or 800 μg/L, and the changes in the neurobehavior of juvenile fish were observed after hatching, including touch-escape reaction at 72 hours after fertilization and autonomic movement and panic es-cape reflex at 7 days after fertilization.@*Results@#Compared with the 0 mg/L group, the≥66.6 mg/L group had a sig-nificant reduction in embryonic hatching rate at 48 and 72 hours after fertilization, and the ≥72.0 mg/L group had a significant increase in embryonic mortality rate at 96 hours after fertilization (P<0.05) . Compared with the 0 μg/L group, the≥100 μg/L group had a significant reduction in the number of times of touch-escape reaction (P<0.05) .Compared with the 0 and 50 μg/L groups, the 100-800 μg/L groups had significant reductions in total movement distance and average speed (P<0.05) . Compared with the dark period before illumination, all groups had a significant increase in movement speed during the light period of the panic escape reflex test (i.e., the third minute) (P<0.05) ; within 2 minutes after the light was turned off, there was no significant change in movement speed in the 0-200 μg/L groups (P>0.05) ; the 400 and 800 μg/L groups had a significant increase in movement speed (P<0.05) .@*Conclusion@#AlCl3 exposure may cause embryonic developmental disorder in zebrafish and ab-normal neurobehavior in juvenile fish.

Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats.</p><p><b>METHODS</b>Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70.</p><p><b>RESULTS</b>No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results.</p><p><b>CONCLUSION</b>Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.</p>

Neurotoxicological effects of deltamethrin on the postnatal development of cerebellum of rat.

Deitamethrin (DLT) has been accepted to be 10,000 times less toxic to man than to insects. While toxicity of DLT in adult animals has been studied using biochemical and electrophysiological tools, reports on its developmental neurotoxicity are rather scanty. Wistar rat pups were exposed to DLT (0·7 mg/kg body wt/day, i.p., dissolved in propylene glycol) from postnatal day 9-13. Equal number of age matched pups were used as vehicle controls. The animals were weighed and perfused intracardially on postnatal days 12, 15, 21, and 30 and their brains dissected out. Cerebellum along with the brainstem was separated by a transverse section at the tectal level and processed for morphometric and toxicological studies. The micro- and inter-neurons in the cerebellum are known to differentiate and mature, both morphologically and biochemically, during the postnatal life of rats. Postnatal exposure to DLT has been observed to delay the cytogenesis and morphogenesis of these neurons. In addition to this, damage to the developing vasculature has also been recorded in the form of thrombus and haemorrhage. Focal degeneration and spongy appearance of the tissue in the vicinity of the damaged blood vessels have also been recorded. The study has opened up several questions on the safety of this substance to the pregnant mothers and infants in the habitats where this substance is in use for vector control.