Cytosine arabinoside induces phosphorylation of histone H2AX in hippocampal neurons via a noncanonical pathway.

Cytosine arabinoside (Ara-C), an anticancer drug, is known to inhibit DNA replication in mitotic cells. Ara-C is also considered to induce DNA damage, leading to neuronal cell death. To identify the mechanism by which Ara-C kills neurons, we assessed the levels of phosphorylated histone H2AX (γ-H2AX), a marker for DNA double-strand breaks (DSBs), in hippocampal neurons cultured for 48 h with Ara-C.

Prenatal and postnatal bisphenol A exposure inhibits postnatal neurogenesis in the hippocampal dentate gyrus.

Bisphenol A (BPA), an endocrine disruptor with estrogenic effects, is widely used as a raw material for manufacturing polycarbonate plastic and epoxy resins. Prenatal and postnatal exposure to BPA affects brain morphogenesis. However, the effects of prenatal and postnatal BPA exposure on postnatal neurogenesis in mice are poorly understood.

Postnatal di-2-ethylhexyl phthalate exposure affects hippocampal dentate gyrus morphogenesis.

Di-2-ethylhexyl phthalate (DEHP) is the most commonly used phthalate for the production of flexible polyvinyl chloride. Recent studies in humans reported a widespread DEHP exposure, raising concerns in infants whose metabolic and excretory systems are immature. DEHP is a potential endocrine-disrupting chemical, but the effects of postnatal DEHP exposure on neuronal development are unclear.

Bacterial SOS Genes Promote Mouse Tumors by Activating Oncogenes via a miR-145 Sponge.

The mechanism of cancer induction involves an aberrant expression of oncogenes whose functions can be controlled by RNAi with miRNA. Even foreign bacterial RNA may interfere with the expression of oncogenes. Here we show that bacterial plasmid and its genomic homolog carrying homologies that match the mouse anti-miR-145, sequestered the miR-145 function in mouse BALB 3T3 cells in a tetracycline (Tet)-inducible manner, activated oncogene and its downstream and further enhanced microcolony formation and cellular transformation as well as the short fragments of the bacterial gene containing the anti-miR-145 sequence.

Maternal administration of bisphenol A alters the microglial profile in the neocortex of mouse weanlings.

Bisphenol A (BPA) is known to cause abnormal neurogenesis in the developing neocortex. The mechanisms of BPA toxicity concerning neuroinflammatory-related endpoints are incompletely characterized. To evaluate the microglial morphology and the gene expression of pro-inflammatory cytokines in the newborn neocortex, ICR mice were exposed to BPA 200 μg/kg/d on gestational day 6 through post-partum day 21.

The neonicotinoids acetamiprid and imidacloprid impair neurogenesis and alter the microglial profile in the hippocampal dentate gyrus of mouse neonates.

Acetamiprid (ACE) and imidacloprid (IMI) are widely used neonicotinoid pesticides. They bind selectively to insect nicotinic acetylcholine receptors (nAChRs) and are considered non-hazardous to mammals. Few studies have assessed the activation of vertebrate nAChRs and the neurodevelopmental toxicity following in utero or neonatal exposure to neonicotinoids; therefore, we evaluated the effects of ACE or IMI exposure on neurogenesis and microglial profiles in the developing hippocampal dentate gyrus (DG) of mouse neonates.

Neurodevelopmental toxicity in the mouse neocortex following prenatal exposure to acetamiprid.

Acetamiprid (ACE) belongs to a widely used class of pesticides known as neonicotinoids. ACE binds selectively to insect nicotinic acetylcholine receptors and was previously considered relatively safe in mammalian species; however, recent studies have demonstrated ACE-mediated toxicity related to vertebrate nicotinic acetylcholine receptor activation. The potential for neurotoxicity following exposure to ACE in utero is unknown.

Exposure to bisphenol A affects GABAergic neuron differentiation in neurosphere cultures.

Endocrine-disrupting chemicals (EDCs) influence not only endocrine functions but also neuronal development and functions. In-vivo studies have suggested the relationship of EDC-induced neurobehavioral disorders with dysfunctions of neurotransmitter mechanisms including γ-aminobutyric acid (GABA)ergic mechanisms. However, whether EDCs affect GABAergic neuron differentiation remains unclear.

Endocrine disrupting chemicals, 4-nonylphenol, bisphenol A and butyl benzyl phthalate, impair metabolism of estradiol in male and female rats as assessed by levels of 15α-hydroxyestrogens and catechol estrogens in urine.

Bisphenol A (BPA), 4-nonylphenol (NP) and butyl benzyl phthalate (BBP), termed endocrine-disrupting chemicals, are known to mimic estrogen activity. The effects of these chemicals on 17β-estradiol (E ) metabolism in vivo in rats were examined. Male and female rats were given NP (250 mg kg  day ), BPA (250 μg kg  day ) or BBP (500 mg kg  day ) by gavage for 14 days, followed by a single intraperitoneal injection of E (5 mg kg ) on the final day.

Mechanisms underlying neuro-inflammation and neurodevelopmental toxicity in the mouse neocortex following prenatal exposure to ethanol.

Fetal alcohol spectrum disorders (FASD) constitute a wide range of disorders that arise from prenatal exposure to ethanol (EtOH). However, detailed reports regarding the adverse effects of prenatal EtOH exposure on neocortical morphology and its underlying pathogenic mechanisms are limited. In the present study, we aimed to characterize the anatomical abnormalities of neocortical development and their correlation with microglial properties and neuro-inflammation in a mouse model of FASD.

Prenatal exposure to di(2-ethylhexyl) phthalate impairs development of the mouse neocortex.

Di(2-ethylhexyl) phthalate (DEHP) is currently the most commonly used phthalate for the production of flexible polyvinyl chloride. Phthalates including DEHP have been labeled as potential endocrine disruptors. The effect on the development of the neocortex, however, is unknown.

Newborn mice exposed prenatally to bisphenol A show hyperactivity and defective neocortical development.

The central nervous system is especially susceptible to toxic insults during development. Prenatal administration of bisphenol A (BPA) induces histologic anomalies in the dorsal telencephalon of the embryo. Whether these anomalies affect the morphogenesis and maturation of neuronal function of the newborn neocortex, however, is unknown.

Long-term pre-exposure of pheochromocytoma PC12 cells to endocrine-disrupting chemicals influences neuronal differentiation.

This study examined the effects of exposure to low concentrations (0.1-100 nM) of bisphenol A (BPA) or nonylphenol (NP) on neuronal differentiation in pheochromocytoma PC12 cells. Pre-exposure to BPA for a week or a month, but not for a day, decreased neuronal differentiation in PC12 cells.

Neurobehavioral evaluation of mouse newborns exposed prenatally to low-dose bisphenol A.

There have been few neurobehavioral toxicology studies on newborn animals. Thus, we developed a mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants, by means of determining the newborn's motor activity applying the tare function of an analytical balance. Motor activities including crawling, pivoting, righting or tremors of mouse newborns were evaluated.

Long-term exposure of 3T3 fibroblast cells to endocrine disruptors alters sensitivity to oxidative injury.

When Swiss 3T3 fibroblasts were exposed to bisphenol A (BPA) or nonylphenol (NP) within a range of 0.1-100 nM for 30-45 days, increased resistance to oxidative injury was found. Western blot analysis indicated concomitant increased expression of bcl-2 protein and reduced histone methylation levels in cells after BPA or NP exposure.

Early to middle gestational exposure to diethylstilbestrol impairs the development of labyrinth zone in mouse placenta.

This study was performed to clarify the involvement of impaired labyrinth zone (LZ) of the placenta in the developmental toxicity of diethylstilbestrol (DES). DES at 10 μg/kg per day was administered orally to mice on days 4 through 8 of gestation. Histological observation of the LZ and determination of blood glucose levels in dam and fetus were performed on day 13.

Newly developed mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of environmental toxicants.

Although there have been a vast number of behavioral toxicology studies carried out on adult mice and rats, there have been few neurobehavioral studies utilizing their newborn animals. Thus, we developed a mouse newborn behavioral testing method for evaluating the risk of neurotoxicity of chemicals, by means of determining the newborn's activity using the tare function of an analytical balance. The unstable weighing values resulting from movement of the newborn on the balance recorded by a personal computer every 0.

Developmental effects of oral exposure to diethylstilbestrol on mouse placenta.

Placental growth and function are of biological significance in that placental tissue promotes prenatal life and the maintenance of pregnancy. Exposure to synthetic estrogens causes embryonic mortality and placental growth restriction in mice. The aim of the present study was to examine the effects of diethylstilbestrol (DES) on placenta in mice.

Maternal bisphenol A oral dosing relates to the acceleration of neurogenesis in the developing neocortex of mouse fetuses.

Bisphenol A (BPA), an endocrine-disruptor, is widely used in the production of plastics and resins. Human perinatal exposure to this chemical has been proposed to be a potential risk to public health. Animal studies indicate that postnatal exposure to BPA may affect neocortex development in embryos by accelerated neurogenesis and causing neuronal migration defects.

Methylnitrosourea induces neural progenitor cell apoptosis and microcephaly in mouse embryos.

Background: Prenatal exposure to methylnitrosourea (MNU), an alkylating agent, induces microcephaly in mice. However, its pathogenetic mechanism has not been clarified, especially that in the development of the cerebral cortex.

Methods: ICR mice were treated with MNU at 10 mg/kg intraperitoneally on day 13.

Early embryonic losses in mice induced by diethylstilbestrol.

Estrogens cause embryonic lethality and the disturbance of early placental development in mice. Diethylstilbestrol (DES) at 1, 10, or 100 microg/kg was orally administered to Institute of Cancer Research mice on gestational days (GD) 4 through 8, and the uterus and placenta were examined histopathologically on GD 9. Decidua of DES-treated mice showed insufficient development, and the uterine lumen at the implantation site did not effectively minimize.

Cardiovascular malformations induced by prenatal exposure to phenobarbital in rats.

The effects of prenatal exposure to phenobarbital (PB) on the cardiovascular system were examined in rat fetuses and pups. PB was administered at a dose of 80 or 120 mg/kg/day by gavage to Sprague Dawley (SD) rats on two consecutive gestational days (GD): 7-8, 8-9, 9-10, or 10-11. Fetuses were examined for cardiovascular malformations on GD 20.

Influence of di-(2-ethylhexyl)phthalate on fetal testicular development by oral administration to pregnant rats.

Influence of di-(2-ethylhexyl)phthalate (DEHP) on testicular development was studied by oral administration of DEHP at doses of 500 and 1000 mg/kg/day to pregnant rats on gestational days (G) 7 to 18. Ethinyl estradiol (EE) at dose levels of 0.25 and 0.

Locomotor hyperactivity following prenatal exposure to 5-bromo-2'-deoxyuridine: neurochemical and behavioral evidence of dopaminergic and serotonergic alterations.

Prenatal exposure to 5-bromo-2'-deoxyuridine (BrdU) has been reported to induce abnormal behaviors in offspring, including marked hyperactivity. In this study, the contribution of the serotonin (5-HT) and dopamine (DA) systems to BrdU-induced developmental neurotoxicity was investigated. Sprague-Dawley rats were treated with BrdU on gestational days 9 through 15 (50mg/kg, i.

Intrauterine position and postnatal growth in Sprague-Dawley rats and ICR mice.

In rodents, steroid hormones are thought to be transported between adjacent fetuses, and male or female fetuses that develop in utero between female fetuses may have higher serum levels of estradiol, and lower serum levels of testosterone, relative to siblings of the same sex that develop between two male fetuses. The consequence in the variation of postnatal growth, development, and function in the intrauterine position, using various parameters such as anogenital distance, preputial separation and vaginal opening, estrous cycle, locomotor activity, and growth of reproductive organs, were examined in Sprague-Dawley rats. ICR mice were treated with 17beta-estradiol before copulation and during pregnancy to address the interaction with endogenous estradiol during pregnancy.