Contaminants in the environment is can cause adverse effects on human and animal health. Persistent organic pollutants (POPs) accumulate in the food chain and has created elevated levels of contaminants in organs, blood serum and breast milk in humans and animals. It has in recent years been a growing interest to investigate whether there is an association between exposure to POPs and brain function. In this project we have special attention paid to the body's responses to stress impact.
Studies are done on both single substances and mixtures of POPs reflecting concentrations measured in humans. In animal experiments with mice, mothers have been exposed to these compounds while their offspring have been examined in terms of learning ability and response to stress. Preliminary results from the behavior studies indicate that mouse pups born under mothers exposed to POPs have lower learning ability. Maternal exposure also affected their hormonal response to stress. This was also reflected in their offspring, but predominantly in males. Further work is focused on trying to elucidate mechanisms by which POPs can affect stress responses and behavior on the molecular level. Brain material has been processed for further analyses and subjected to gene Expression analyses.
In cell models are similar mixtures and single substances investigated, in order to study the mechanisms of action. It is shown that the mentioned POP mixes induce ROS (Reactive Oxygen Species) formation and that single compounds, particularly perfluorinated compounds are neurotoxic. This effect is dependent on the number of carbon atoms in the molecule and its functional group. Moreover, it is shown that PFOS acts via the NMDA receptor. Mixed exposures of nerve cells with different halogenated compounds have demonstrated antagonistic and additive effects. The same cells have also been used for exposures with defined mixes of POPs similar to those used for exposures of live animals. The results indicated that concentrations close to human relevant levels caused ROS-formation and affected genes important for neuronal function.
Mixes of POPs have been used for exposure of liver cells and transfected cells indicating binding of pollutants to hormone receptors (glucocorticoid receptor) by Queens University, Belfast, with the purpose of developing a HCA system (High Content Analysis system) for toxicity assessment. Two scientific publications have been published based on the HCA results. In addition, effects of DDT-metabolites with potential adrenotoxic potential has been investigated in primary endocrine cells from pig testicles.
The mixes mentioned above have also been used by University of Bergen for studies on the steroidogenesis in human adrenocortical cells. The results shows that mixes of POPs relevant for human exposure affects hormone secretion in these cells.
Research on combination effects of persistent organic pollutants (POPs) and methods for a systematic approach are required for an improved risk-assessment of health- and environment damaging chemicals.
The behavioral and physiological traits of an indiv idual are strongly influenced by early life events. One of the major systems implicated in the responses to environmental manipulations and stress is the Hypothalamus-Pituitary-Adrenal (HPA) axis. Glucocorticoid hormones (cortisol in humans and corticoste rone in rodents) represent the final step in the activation of the HPA axis and play an important role in effects induced by the perinatal environment.
Changes in the function of the HPA-axis may lead to altered stress responses and changes in cognitive functions. This project hypothesize that exposure with POPs and mixtures thereof, reflecting natural exposure scenarios, affect cell functions of endocrine cells in the HPA-axis and that these compounds, when used for exposure during foetal development in a sensitive rodent model, induce long-term effects on cognitive functions and stress responses in adult life.
Effects will be studied in both complex organisms and cell cultures to shed light both on potential mechanisms and on the real life situation . To explore this chain of events we will study the effects of different POPs, alone or in combination with phthalates, bisphenol A and perfluorinated compounds.