Effects of Environmentally Relevant Mixtures of Persistent Organic Pollutants on the Developmental Neurobiology in Rats

Abstract

We report the developmental neuropathology for rat pups at postnatal day (PND) 37 and PND 77 and the molecular biomarkers for PND 35, 75, and 350 after perinatal exposure to a reconstituted mixture of persistent organochlorine pollutants (POPs) based on the blood profiles of people living in the Great Lake Basin. The developmental neuropathology included routine histopathology evaluation, quantification of cell proliferation and death in the subventricular zone, linear morphometric measurements, and transcriptional analysis. No histopathological, structural, or stereological changes were observed in animals treated with the POPs or Aroclor 1254, on PND 37 or PND 77. While no transcriptional changes were found in Arcolor-treated animals, significant transcriptional changes were observed on PND 350 in female offspring perinatally exposed to 0.13 mg/kg of the POP mixture. Markers of the cholinergic system including acetylcholinesterase and the muscarinic receptors (subtypes M1-M5) were downregulated 2- to 6-fold. In addition, structural genes including neurofilaments (NFLs) and microtubule-associated protein (MAP-2) were downregulated at least 2-fold or greater. Our results support that in utero and lactational exposure to the chemical mixture of POPs lead to developmental changes in adult rat brains.

Developmental neurotoxicity of polybrominated diphenyl ethers mixture de71 in Sprague-Dawley rats

“…The upregulation of markers represents a compensatory effect after lactational exposure and may be attributed to continued residual presence or exposure of DE71 at this this stage. At PND 250, downregulation of the cholinergic system in both male and female offspring suggests that exposure to DE71 during rapid development of the neonatal rat brain leads to irreversible alterations in the function of the adult, as reported previously (Gill et al, 2013). At PND 50 and PND 105, the effects observed at PND 21 may be masked due to the reserve capacity and plasticity of the brain (Forcelli et al, 2011;Slikker and Boyer, 2005), with the masking depleted over time by a number of factors, such as aging.…”

“…All cycles chosen were in the range of the linear relationship between the PCR products and number of cycles (Marone et al, 2001). The cDNA products were separated on a 2% agarose gel (Marone et al, 2001;Gill et al, 2013). The internal house-keeping gene for semiquantitative PCR analysis was 18S (3:7 alt RNA) (Applied Biosystems) since its expression did not change with the different treatment groups.…”

Canadian Arctic Contaminants and Their Effects on the Maternal Brain and Behaviour: A Scoping Review of the Animal Literature

“…Many researchers have explored the impact of the abovementioned pollutants on the neurological health of offspring [52][53][54][55]. Considering the sensitive period of in utero development, studies have focused on developmental outcomes following toxicant exposure.…”

Developmental neurotoxicity of succeeding generations of insecticides

“…Pre and postnatal exposure to a mixture of OC insecticides that includes DDT, dieldrin and aldrin evokes robust reductions in gene expression for muscarinic cholinergic receptors (mAChR) and acetylcholinesterase that persists into adulthood in female rats (Gill and others 2013). Similarly, DDT exposure during the neonatal period evokes downregulation of muscarinic acetylcholine receptors (Eriksson and others 1992).…”