Effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on fetal brain growth and motor and behavioral development in offspring rats

Nishijo, Muneko; Kuriwaki, Jun-Ichi; Hori, Etsuro; Tawara, Kenji; Nakagawa, Hideaki; Nishijo, Hisao

doi:10.1016/j.toxlet.2007.06.007

Cited by 69 publications

(40 citation statements)

References 24 publications

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“…AHR is a highly conserved transcription factor ubiquitously expressed in the brain, whose most potent ligand and activator is 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), a common industrial pollutant (Abel and Haarmann-Stemmann, 2010). Rodents exposed to TCDD during neurodevelopment exhibit deficits in working memory (Seo et al, 1999), delayed alternation tasks (Markowski et al, 2002), and emotional learning (Nishijo et al, 2007). Disturbances in social interaction, an effect that is more pronounced in male animals, is associated with alterations in Ca 2+ /calmodulindependent protein kinase IIα (CaMKIIα) (Nguyen et al, 2013a), a regulator of GABAergic neurotransmission (Guetg et al, 2010;Houston et al, 2009).…”

Section: Aryl Hydrocarbon Receptor Signalingmentioning

confidence: 99%

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: Potential roles in GABAergic interneuron pathology

Schubert¹,

Föcking²,

Cotter³

2015

Schizophrenia Research

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Section: Aryl Hydrocarbon Receptor Signalingmentioning

confidence: 99%

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: Potential roles in GABAergic interneuron pathology

Schubert¹,

Föcking²,

Cotter³

2015

Schizophrenia Research

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“…During brain development, the AhR homologues in Drosophila, Spineless (Ss), and in Caenorhabditis elegans, ahr-1, regulate the diversification of dendrite morphology (Kim et al 2006), neuronal differentiation (Qin and Powell-Coffman 2004), and specify the cell fate of GABAergic neurons (Huang et al 2004). Toxicological and epidemiological studies revealed that exposure to environmental AhR ligands are associated with delayed development of brain sexual dimorphism, social behavior, learning ability, and neuropsychiatric disorders in both animal models and humans (Ikeda et al 2005;Nishijo et al 2007;Piedrafita et al 2008;Patandin et al 1999;Goetz et al 1994). Although AhR-mediated neurotoxicity has been demonstrated in various experimental systems (Kim and Yang 2005;Akahoshi et al 2006;Lin et al 2008), information were limited to its up-regulation of CYP1A1 and oxidative stress.…”

mentioning

confidence: 99%

Knockdown of the aryl hydrocarbon receptor attenuates excitotoxicity and enhances NMDA‐induced BDNF expression in cortical neurons

Lin

Chen

Chou

et al. 2009

Journal of Neurochemistry

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NMDA receptors play dual and opposing roles in neuronal survival by mediating the activity‐dependent neurotrophic signaling and excitotoxic cell death via synaptic and extrasynaptic receptors, respectively. In this study, we demonstrate that the aryl hydrocarbon receptor (AhR), also known as the dioxin receptor, is involved in the expression and the opposing activities of NMDA receptors. In primary cultured cortical neurons, we found that NMDA excitotoxicity is significantly enhanced by an AhR agonist 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin, and AhR knockdown with small interfering RNA significantly reduces NMDA excitotoxicity. AhR knockdown also significantly reduces NMDA‐increases intracellular calcium concentration, NMDA receptor expression and surface presentation, and moderately decreases the NMDA receptor‐mediated spontaneous as well as miniature excitatory post‐synaptic currents. However, AhR knockdown significantly enhances the bath NMDA application– but not synaptic NMDA receptor‐induced brain‐derived neurotrophic factor (BDNF) gene expression, and activating AhR reduces the bath NMDA‐induced BDNF expression. Furthermore, AhR knockdown reveals the calcium dependency of NMDA‐induced BDNF expression and the binding activity of cAMP‐responsive element binding protein (CREB) and its calcium‐dependent coactivator CREB binding protein (CBP) to the BDNF promoter upon NMDA treatment. Together, our results suggest that AhR opposingly regulates NMDA receptor‐mediated excitotoxicity and neurotrophism possibly by differentially regulating the expression of synaptic and extrasynaptic NMDA receptors.

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“…We have also reported that maternal exposure to 2,3,7,8-TCDD during pregnancy significantly delays fetal brain growth and affects the active avoidance behavior of rat offspring during the growth period [34]. In particular, we found a developmental delay in the forebrain, which suggests that 2,3,7,8-TCDD affects the limbic system, which in turn plays an important role in avoidance behaviors [34]. A functional change in the limbic system can induce not only learning deficits but also emotional disturbances, and 2,3,7,8-TCDD may therefore affect both the emotional development and cognitive development of the human infant.…”

Section: Discussionmentioning

confidence: 86%

Effects of maternal dioxin exposure on newborn size at birth among Japanese mother–infant pairs

Tawara

Nishijo

Honda

et al. 2008

Environ Health Prev Med

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Objective Maternal exposure to dioxins [polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (DFs)] during pregnancy is known to affect infant growth and neurodevelopment in humans and animals. The aim of this study was to investigate the relationship between newborn size and the concentration of dioxin isomers in breast milk and to subsequently evaluate the potential toxicity of each dioxin isomer among mothers living in sea coast areas who are at a high risk of contamination due to a high consumption of fish. Methods A total of 75 milk samples were obtained within 1 month of delivery from Japanese mothers living in the coastal areas of the Japan Sea. The relationships between the levels of seven dioxins and ten furan isomers in maternal breast milk, measured by high-resolution-gas chromatography/mass spectrometry, and the birth size of newborns, which is related to fetal growth, were investigated after adjustment for confounding factors. Results The concentrations of 1,2,3,6,7,8-HxCDD (hexachlorodibenzo-p-dioxin), 2,3,4,7,8-PeCDF (pentachlorodibenzofuran), 2,3,4,6,7,8-HxCDF, and three dioxin toxic equivalent (TEQ) levels (PCDDs-TEQ, PCDFs-TEQ, and total-TEQ) in maternal breast milk were inversely correlated to newborn length even after adjustment for gestational weeks, infant sex, and maternal age and height. These isomers were abundant among the 17 isomers tested and reflected the TEQ levels. Only 2,3,7,3,7,, the most toxic isomer, was negatively correlated with newborn head circumference, even after adjustment for gestational weeks, infant birth weight, and other confounding factors. Conclusions Based on our results, fetal growth may be influenced by maternal total exposure to dioxins, but only exposure to 2,3,7,8-TCDD would appear to possibly affect fetal head size during pregnancy.

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Effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on fetal brain growth and motor and behavioral development in offspring rats

Cited by 69 publications

References 24 publications

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: Potential roles in GABAergic interneuron pathology

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: Potential roles in GABAergic interneuron pathology

Knockdown of the aryl hydrocarbon receptor attenuates excitotoxicity and enhances NMDA‐induced BDNF expression in cortical neurons

Effects of maternal dioxin exposure on newborn size at birth among Japanese mother–infant pairs

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