Background: Prenatal polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) exposures may influence children’s neurodevelopment. Objective: We examined the association of prenatal PBDE and PCB exposures with children’s reading skills at ages 5 and 8 years, Full-Scale Intelligence Quotient (FSIQ), and externalizing behavior problems at age 8 years. Methods: From 239 mother–child pairs recruited (2003–2006) in Cincinnati, Ohio, we measured maternal serum PBDE and PCB concentrations, assessed child’s reading skills using the Woodcock–Johnson Tests of Achievement III (WJ-III) at age 5 years and the Wide Range Achievement Test-4 (WRAT-4) at age 8 years, tested FSIQ using the Wechsler Intelligence Scale for Children-IV (WISC-IV), and externalizing behavior problems using the Behavioral Assessment System for Children-2 (BASC-2) at age 8 years. We used multiple linear regression to examine the association of prenatal PBDE and PCB concentrations and reading, FSIQ, and externalizing behavior problems after adjusting for covariates. Results: An increase of Sum4PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) by 10 times was not significantly associated with reading scores at age 5 years at the p = 0.05 level but was inversely associated with Reading Composite scores (β: –6.2, 95% CI: –11.7, –0.6) and FSIQ (β: –5.3, 95% CI: –10.6, –0.02) at age 8 years; it was positively associated with the score for externalizing behavior problems (β: 3.5, 95% CI: –0.1, 7.2) at age 8 years. Prenatal Sum4PCBs (PCB-118, -153, -138-158, and -180) was not significantly associated with a child’s reading skills, FSIQ, and externalizing behavior problems. Conclusion: Prenatal PBDE concentration was inversely associated with reading skills and FSIQ and positively associated with externalizing behavior problems at age 8 years. No significant associations were found in prenatal PCB concentration. Citation: Zhang H, Yolton K, Webster GM, Sjödin A, Calafat AM, Dietrich KN, Xu Y, Xie C, Braun JM, Lanphear BP, Chen A. 2017. Prenatal PBDE and PCB exposures and reading, cognition, and externalizing behavior in children. Environ Health Perspect 125:746–752; http://dx.doi.org/10.1289/EHP478

Humanin (HN) is a novel 24-amino acid peptide that protects neurons against N-methyl-d-aspartate (NMDA)-induced toxicity. However, the contribution of the different mitogen-activated protein kinases (MAPKs) signals to HN neuroprotection against NMDA neurotoxicity remains unclear. The present study was therefore aimed to investigate neuroprotective mechanisms of HN. We analyzed intracellular Ca²⁺ levels, reactive oxygen species (ROS) production, and the MAPKs signal transduction cascade using an in vitro NMDA-mediated excitotoxicity of cortical neurons model. Results showed that: (1) HN attenuated NMDA-induced neuronal insults by increasing cell viability, decreasing lactate dehydrogenase (LDH) release, and increasing cell survival; (2) HN reversed NMDA-induced increase in intracellular calcium; (3) pretreatment by HN or 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator, decreased ROS generation after NMDA exposure; (4) administration of HN or N-Acetyl-l-cysteine (NAC), a ROS scavenger, inhibited NMDA-induced JNK and p38 MAPK activation. These results indicated that HN reduced intracellular elevation of Ca²⁺ levels, which, in turn, inhibited ROS generation and subsequent JNK and p38 MAPK activation that are involved in promoting cell survival in NMDA-induced excitotoxicity. Therefore, the present study suggests that inhibition of ROS-dependent JNK/p38 MAPK signaling pathway serves an effective strategy for HN neuroprotection against certain neurological diseases.

Benzo[a]pyrene (B[a]P), a well-known carcinogen, is widespread in the environment. Although the neurotoxic effect of B[a]P has not drawn much attention, toxic effects of B[a]P on learning and memory have been reported. Since it is well known that neuronal apoptosis plays a major role in impairment of learning and memory triggered by many stimuli, an effort has been made to examine whether the B[a]P-induced neurotoxicity occurs through mitochondria-mediated apoptosis. Cultured newborn rat cerebral neurons were used to clarify the apoptosis induced by B[a]P in the study. After incubating with different doses of B[a]P in presence of S9 for 40 h, the apoptotic rates of B[a]P-treated neurons increased in a dose-dependent manner. Further analysis showed that B[a]P-induced apoptosis was accompanied by loss of mitochondrial membrane potential, release of cytochrome c from mitochondria to the cytosol, downregulation of antiapoptotic protein B-cell lymphoma-2 (Bcl-2) levels with concurrent upregulation in proapoptotic Bcl-2-associated X protein (Bax) levels, and increase in the levels and activities of caspases-9 and -3. However, there was no difference in the activity of caspase-8 between B[a]P-exposed neurons and controls. Collectively, these results showed that B[a]P upregulates Bax and downregulates Bcl-2 expression in cultured cerebral neurons, which leads to mitochondrial release of cytochrome c, caspase-3 activation and neuronal apoptotic death.

Purpose: To investigate whether caffeic acid phenethyl ester (CAPE) has a protective effect on retinal ischemia/reperfusion (I/R) injury in rats, and to determine the possible antioxidant mechanisms. Methods: Seventy-six female Wistar rats were randomized evenly into Sham, I/R injury model (M group), model plus vehicle (MV), and model plus CAPE (MC) groups. Retinal ischemia/reperfusion injury was induced by increasing the intraocular pressure to 110 mmHg for 60 min. Rats in the MV and MC groups were injected with vehicle and CAPE (10 µmol/kg i.p.), respectively, before reperfusion and once a day for one or seven days after I/R. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the retinal tissues were determined 24 hr after I/R. Retinal cells apoptosis was detected 24 hr after I/R injury by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling staining. On day 7 after reperfusion, the electroretinogram (ERG) was recorded, and the retinal histology was examined and quantified using light microscopy. Results: CAPE significantly decreased the MDA levels and increased the activities of SOD, GSH-Px, and CAT in the retina compared with the ischemia group (p < 0.05). CAPE attenuated the I/R-induced apoptosis of retinal cells in the inner nuclear and ganglion cells of the rat retina. CAPE also suppressed the I/R-induced reduction in the a- and b-wave amplitudes of the ERG (p < 0.05). The thickness of the entire retina, inner nuclear layer, and inner plexiform layer and the number of cells in the ganglion cell layer in the MC group were significantly greater than those in the M group (p < 0.05). Conclusions: CAPE can protect the rat retina from I/R injury by enhancing the antioxidation ability and inhibiting the apoptosis of retinal cells, which suggests that CAPE is potentially useful for treating I/R-induced eye disorders.