Tetrachlorodibenzo‐p‐dioxin exposure alters radial arm maze performance and hippocampal morphology in female AhR ^+/– mice

Abstract

Perinatal exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) has been reported to alter spatial learning in rats tested on a radial arm maze (RAM). TCDD is believed to exert most of its effects through binding to the aryl hydrocarbon receptor (AhR). To determine whether the AhR mediates TCDD‐induced alterations in spatial learning, we tested male and female AhR‐knockout (AhR –/–), heterozygous (AhR +/–) and wild‐type (AhR +/+) mice on the RAM. AhR +/– male and female mice were time mated, and treated dams were dosed with 5 μg TCDD/kg body weight on day 13 of gestation. When offspring reached adulthood, male and female AhR +/+, AhR +/– and AhR –/– mice from TCDD‐exposed and unexposed litters were tested on the eight‐arm RAM. After testing, we examined hippocampal morphology as visualized by the Timm's silver sulfide stain. TCDD‐exposed female AhR +/– mice made more errors than their respective controls on the RAM and exhibited a decrease in the size of the intra‐ and infrapyramidal mossy fiber (IIP‐MF) field of the hippocampus. None of the other TCDD‐exposed groups differed from their respective control groups with regard to maze performance or hippocampal morphology. The reduction of IIP‐MF field indicates a possible morphological basis for the learning deficit that was observed in the female AhR +/– mice. It is hypothesized that the effect of TCDD exposure is AhR dependent and that TCDD may alter GABAergic activity in the hippocampus of female mice during development.

Organohalogen contaminants and metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins and Atlantic white-sided dolphins from the western North Atlantic

“…The mechanisms of PCB neurotoxicity most likely involve multiple modes of action, which largely depend upon the congener structure. The mechanisms include effects on thyroid hormone dependent neurodevelopment (Zoeller et al, 2002); binding to and activation of the aryl hydrocarbon receptor (AhR) by planar PCBs by a mechanism similar to that of dioxin (Collins et al, 2008;Powers et al, 2005); impairment of the function of glutamate-nitric oxide-cGMP pathway (Piedrafita et al, 14 2008); effects on brain cholinergic muscarinic receptors (Coccini et al, 2006); and damage to dopaminergic neurons (Seegal et al, 2002). In our study, CB-153 (a PCB congener with a non-planar structure) was the most abundant PCB congener in CSF and cerebellum GM.…”

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

“…Activation of AhR by these environmental toxins leads to cytotoxicity and carcinogenesis via induction of cytochrome P450 1A1/1A2 expression that generates toxic metabolites and induces oxidative stress (Nebert et al 2004). In mammalian brains, AhR is widely expressed in the cerebral cortex, hippocampus, hypothalamus, brainstem, and cerebellum (Petersen et al 2000;Powers et al 2005;Lin et al 2008). Information regarding the physiological roles of AhR in the brain is limited.…”

The Aryl Hydrocarbon Receptor sans Xenobiotics: Endogenous Function in Genetic Model Systems

“…However, no studies have yet been conducted into AHR function in these tissues. Moreover, the only studies into AHR function with regard to vertebrate neuronal development, a principal theme in invertebrate biology, have been conducted in the framework of xenobiotic toxicity (Hays et al, 2002;Hill et al, 2003;Carvalho and Tillitt, 2004;Powers et al, 2005;Williamson et al, 2005;Hood et al, 2006;Petersen et al, 2006).…”