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

Estimation of in vivo and in vitro exposure to bisphenol A as food contaminant

“…Based on the EC 50 values, BPA was only one to two orders of the magnitude (10e100 fold) less toxic than highly cytotoxic drug Doxorubicin ® and 30e300 fold more toxic compared to Aspirin ® (Table 3). Numerous the in vitro (Hanioka et al, 2008;Le Corre et al, 2013) and the in vivo studies (Komada et al, 2014;Song et al, 2014) reported that BPA had adverse effects at lower concentrations than it was in the no observed adverse effect levels (NOAELs) of 5e50 mg/kg/day, established in the regulatory toxicity studies that are used for human risk assessment (FitzGerald and Wilks, 2014). Qian et al (2014) provided the insight into the BPAinduced reproductive toxicity in mouse Sertoli cell line TM4.…”

“…After an acute BPA exposure, a dose-and time-dependent suppression of cell viability was reported as well as the mitochondrial mass loss, the membrane potential decrease, cytochrome c release, Bcl-2 family down regulation and caspase-3 up regulation, all resulting in the BPA-induced cell apoptosis (Qian et al, 2014). Prenatal BPA exposure induced neurobehavioral toxicity associated with abnormal dopaminergic neuronal projections and abnormal corticogenesis and lamination in newborn mice (Komada et al, 2014). Oxidative and pro-inflammatory damage to the rat hepatocytes (in vitro and in vivo) induced by BPA was proved by Moon et al (2012).…”

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

“…2). Of particular note, some research has indicated that abnormal neocortical layer structure reduces dopaminergic neuronal projections in the prefrontal cortex of bisphenol A-treated and Smoothened conditional knockout mice 23, 24 . The mesocortical dopaminergic pathway (substantia nigra-prefrontal cortex) controls the reward system of the brain as well as behavior 16, 25, 26 .…”

“…Cells were quantified using Adobe Photoshop CS4 software (Adobe, San Jose, CA, USA), as previously described 24 . In the dorsal telencephalon/neocortex, cells positive for ionized calcium-binding adapter molecule 1 (Iba1), 5-chloro-2′-deoxyuridine (CldU), 5-iodo-2′-deoxyuridine (IdU), antigen KI-67 (Ki67), nuclear receptor related 1 (Nurr1), cut-like homeobox 1 (Cux1), transducin-like enhancer of split 4 (Tle4), CD206, CD11b, active & pro caspase-3, and 4′,6-diamidino-2-phenylindole (DAPI) were manually counted.…”

GABAA overactivation potentiates the effects of NMDA blockade during the brain growth spurt in eliciting locomotor hyperactivity in juvenile mice

“…For instance, the blockade of NMDAR or the overactivation of GABAAR in immature neurons, even at concentrations that are too low to induce apoptosis, impairs neuronal differentiation and reduces synapse integrity (Sinner et al, 2011a,b); dysregulates several proteins involved in neuronal migration, axon growth and guidance (Kaindl et al, 2008) and promotes alterations in lamination and heterotopic cell clusters (Heck et al, 2007;Reiprich et al, 2005) in the rodent cerebral cortex. Most of these effects have been directly or indirectly associated with an increase in locomotor activity (Casanova, 2014;Drerup et al, 2010;Komada et al, 2014;Shin et al, 2004).…”