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Polychlorinated biphenyls (PCBs) are toxic environmental pollutants. Humans are exposed to PCB mixtures via contaminated food or water. PCB exposure causes adverse effects in adults and after exposure in utero. PCB toxicity depends on the congener mixture and CYP1A2 gene activity. For coplanar PCBs, toxicity depends on ligand affinity for the aryl hydrocarbon receptor (AHR). Previously, we found that perinatal exposure of mice to a three‐coplanar/five‐noncoplanar PCB mixture induced deficits in novel object recognition and trial failures in the Morris water maze in Cyp1a2−/−::Ahrb1 C57BL6/J mice compared with wild‐type mice (Ahrb1 = high AHR affinity). Here we exposed gravid Cyp1a2−/−::Ahrb1 mice to a PCB mixture on embryonic day 10.5 by gavage and examined the F1 and F3 offspring (not F2). PCB‐exposed F1 mice exhibited increased open‐field central time, reduced acoustic startle, greater conditioned contextual freezing and reduced CA1 hippocampal long‐term potentiation with no change in spatial learning or memory. F1 mice also had inhibited growth, decreased heart rate and cardiac output, and impaired fertility. F3 mice showed few effects. Gene expression changes were primarily in F1 PCB males compared with wild‐type males. There were minimal RNA and DNA methylation changes in the hippocampus from F1 to F3 with no clear relevance to the functional effects. F0 PCB exposure during a period of rapid DNA de‐/remethylation in a susceptible genotype produced clear F1 effects with little evidence of transgenerational effects in the F3 generation. While PCBs show clear developmental neurotoxicity, their effects do not persist across generations for effects assessed herein. We hypothesized that prenatal exposure to polychlorinated biphenyls (PCBs) at a time of DNA de‐/remethylation would induce F1 neurological and cardiac deficits that would be transmitted epigenetically across generations and be evident in the F3 generation as changes in behavior, hippocampal CA1 long‐term potentiation, cardiac function, RNA expression and DNA methylation. We chose Cyp1a2−/−::Ahrb1 mice because these alleles confer increased susceptibility to PCBs (Ahrb1 has high affinity for the aryl hydrocarbon receptor). F1 PCB‐exposed mice showed behavioral, long‐term potentiation and cardiac functional deficits, but these effects were not recapitulated in F3 mice, nor were there consistent F1 to F3 effects on hippocampal RNA expression or DNA methylation. [ABSTRACT FROM AUTHOR]

Deltamethrin (DLM) is a commonly used pesticide that helps to control crop destruction, disease, and nuisance insects. In rodents DLM can produce choreoathetosis, salivation, and decreased acoustic startle responses (ASR). Herein, adult Sprague Dawley rats were assessed for ASR 2 h after DLM delivered in 5 ml/kg corn oil, however no decrease was observed. Therefore, a test-retest protocol was used to reduce variability, and the effects on ASR on postnatal day 15 (P15) and adult rats were assessed 2, 4, 6, and 8 h after DLM administration (0, 1, 2, or 4 mg/kg for P15 rats and 0, 2, 8, or 25 mg/kg for adults). In a separate set of rats identically treated, DLM levels were determined in blood and brain. DLM (8 or 25 mg/kg) in adult rats decreased ASR up to 4 h, whereas in P15 rats decreases were observed between 2 and 8 h. The adult 25 mg/kg group showed consistent signs of salivation and tremor, whereas in P15 rats salivation was observed in the 2 and 4 mg/kg groups and tremor was observed at all doses over the 8-h period. Mortality was observed in all P15 dose groups but not in adults. Dose-dependent increases of DLM in blood and brain regardless of age were observed. At approximately equivalent whole brain concentrations, effects were more pronounced in P15 rats than in adult rats. Comparable brain levels of DLM do not explain differences in ASR and tremor between the P15 and adult rats. These data indicate age-dependent differences in sensitivity to DLM. [ABSTRACT FROM AUTHOR]

The intercalated cells (ITCs) of the amygdala have been shown to be critical regulatory components of amygdalar circuits, which control appropriate fear responses. Despite this, the molecular processes guiding ITC development remain poorly understood. Here we establish the zinc finger transcription factor Tshz1 as a marker of ITCs during their migration from the dorsal lateral ganglionic eminence through maturity. Using germline and conditional knock-out (cKO) mouse models, we show that Tshz1 is required for the proper migration and differentiation of ITCs. In the absence of Tshz1, migrating ITC precursors fail to settle in their stereotypical locations encapsulating the lateral amygdala and BLA. Furthermore, they display reductions in the ITC marker Foxp2 and ectopic persistence of the dorsal lateral ganglionic eminence marker Sp8. Tshz1 mutant ITCs show increased cell death at postnatal time points, leading to a dramatic reduction by 3 weeks of age. In line with this, Foxp2-null mutants also show a loss of ITCs at postnatal time points, suggesting that Foxp2 may function downstream of Tshz1 in the maintenance of ITCs. Behavioral analysis of male Tshz1 cKOs revealed defects in fear extinction as well as an increase in floating during the forced swim test, indicative of a depression-like phenotype. Moreover, Tshz1 cKOs display significantly impaired social interaction (i.e., increased passivity) regardless of partner genetics. Together, these results suggest that Tshz1 plays a critical role in the development of ITCs and that fear, depression-like and social behavioral deficits arise in their absence. [ABSTRACT FROM AUTHOR]

The NCTR Collaborative Behavioral Teratology Study (CBTS) data have been reanalyzed by Tachibana (1989) using the strength of association statistic [eta] as a means of examining the reliability of the data. This is an important issue, because determining the reliability of behavioral teratological measures was one of the CBTS's principal aims. The [eta] approach is a useful one, but its value is critically dependent on the assumption that it is applied to the data appropriately. The CBTS was a project which involved large numbers of pregnant rats and their offspring, tested postnatally on a large number of physical and behavioral tests. The project was conducted in six laboratories and involved two experiments with four treatment groups/experiment, 16 dams/group, and 8 offspring/dam. For practical more than theoretical reasons, each of these large experiments was conducted in balanced replicates of 4 dams/group. Since this had to be done, replicate was included in the statistical models used to evaluate the data. Tachibana (1989) has performed a series of [eta] analyses on the CBTS data as if each replicate constituted an independent experiment and concluded that the reproducibility of the CBTS data was not particularly good. Tachibana's [eta] analyses are discussed as problematic because the data should have been analyzed as intended, by experiment (n = 16/group), not by replicates. There are well-known problems associated with the reliability of small sample sizes in any experiment and Tachibana's conclusion, based as it is on replicates, offers little insight into the reproducibility of behavioral teratogenicity data generally or from the CBTS project specifically.