Developmental exposure to the organochlorine insecticide endosulfan alters expression of proteins associated with neurotransmission in the frontal cortex

Abstract

Exposure to environmental contaminants, such as organochlorine insecticides during critical periods of neurodevelopment has been shown to be a major contributor to several neuropsychological deficits seen in children, adolescence, and adults. Although the neurobehavioral outcomes resulting from exposure to these compounds are known the neurotransmitter circuitry and molecular targets that mediate these endpoints have not been identified. Given the importance of the frontal cortex in facilitating numerous neuropsychological processes, our current study sought to investigate the effects of developmental exposure to the organochlorine insecticide, endosulfan, on the expression of specific proteins associated with neurotransmission in the frontal cortex. Utilizing in vitro models we were able to show endosulfan reduces cell viability in IMR-32 neuroblastoma cells in addition to reducing synaptic puncta and neurite outgrowth in primary cultured neurons isolated from the frontal cortex of mice. Elaborating these findings to an in vivo model we found that developmental exposure of female mice to endosulfan during gestation and lactation elicited significant alterations to the GABAergic (GAT1, vGAT, GABAA receptor), glutamatergic (vGlut and GluN2B receptor), and dopaminergic (DAT, TH, VMAT2, and D2 receptor) neurotransmitter systems in the frontal cortex of male offspring. These findings identify damage to critical neurotransmitter circuits and proteins in the frontal cortex, which may underlie the neurobehavioral deficits observed following developmental exposure to endosulfan and other organochlorine insecticides.

Selective damage to dopaminergic transporters following exposure to the brominated flame retardant, HBCDD

“…While HBCDD treatment resulted in a significant loss of TH+ neurons, HBCDD also caused a reduction in the length and complexity of the TH+ neurite outgrowths that arise from the cell body and are involved in mediating synapse formation and communication with adjacent neurons. Like our SK-N-SH data, these findings are congruent with our previously published observations of PBDE-mediated neurotoxicity in TH+ neurons and follow with additional studies in our lab that have paired primary cultured neurons with high content analysis to delineate specific alterations in neuronal morphology (Bradner et al, 2013a, Bradner et al, 2013b, Wilson et al, 2014a, Wilson et al, 2014b). It should be appreciated that our findings do not suggest that HBCDD-mediated neurotoxicity is selective for dopaminergic neurons and endpoints.…”

The seluang fish (Rasbora spp.) diet to improve neurotoxicity of endosulfan-induced intrauterine pup's brain through of oxidative mechanism

“…Exposure to endosulfan during pregnancy and lactation in female rats can affect the neurotransmitter; g-aminobutyric acid (GABA), glutamate, serotonin and dopamine [14,15]. These findings suggested that neurotransmitter disorders may cause neurobehavior disorders caused by endosulfan exposure [15].…”

This can't be stressed enough: The contribution of select environmental toxicants to disruption of the stress circuitry and response

“…Beyond the striatum, evidence is emerging that shows exposure to organochlorines can have significant effects on the mesocortical dopamine pathway. Using a developmental exposure to 500 μg/kg endosulfan throughout gestation and lactation, our group found a significant reduction in the expression of the dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the frontal cortex of 4 month old male offspring (89). …”