Thesis (MA(Research Psychology))-University of Pretoria, 2007. / Abstract in English. Includes bibliographical references.

Thesis (Ph. D.)--Auburn University. / Abstract. Vita. Includes bibliographical references.

Thesis (D.Psych.)--Murdoch University, 2009. / Thesis submitted to the Faculty of Health Sciences. Includes bibliographical references.

Insects have evolved various physiological responses to cope with stressors such as pathogens, toxins and environmental factors. It is known that the responses resulting from infection or DNA damage share some of the same pathways. Exposure of Drosophila melanogaster and the dung beetle Euoniticellus intermedius to stress led to changes in the expression of proteins involved in metabolism, development, protein degradation, mRNA processing and stress responses. Stress responses in D. melanogaster are well characterised. However, the role played by Drosophila p53 (Dmp53) and a member of the retinoblastoma binding protein 6 (RBBP6) family, Snama, are unknown. Snama has been proposed to play a role in Dmp53 regulation. Following DNA damage we investigated the role of Dmp53 and Snama. Flies recovering from camptothecin treatment display a glycolytic flux, involving a metabolic shift, different to that observed in cancer cells. Camptothecin treatment leads to an increase in the mortality of both sexes. Furthermore, females show a specific decrease in fecundity which is due to an increase in Dmp53 dependent apoptosis in the ovaries and is accompanied by a depletion of Snama and an increase in Dmp53 transcripts. Expression data indicated that Dmp53 activity may be largely regulated at the protein level. Bypassing glycolysis through methyl pyruvate supplementation led to differential expression of Dmp53 and Snama and improved reproduction and embryonic development. These results highlight differences between the metabolic strategies used by cancerous and non-cancerous cells which may be exploited in future chemotherapies. While immune responses amongst insect orders are evolutionarily conserved, many remain uncharacterised. To investigate the immune system of an organism that lives in a microbe rich environment, E. intermedius was infected with the fungal pathogen Beauveria bassiana. This resulted in decreased lifespan and fecundity. Homologs of proteins involved in the immune response of insects were identified in E. intermedius, including a member of the Toll family of proteins, an insect defensin (present in the hemolymph) as well as a homolog of the serine protease Persephone. These results show that immune signalling pathways are conserved in this dung beetle.

Numerous medical and environmental toxicology studies have established a link between lead (Pb) exposure, crime, and delinquency. In human environments, lead pollution- like crime- is unequally distributed, creating lead hot spots. In spite of this, studies of crime hotspots have routinely focused on traditional sociological predictors of crime, leaving environmental predictors of crime like lead and other neurotoxins relatively unaddressed. This study attends to this gap in the literature by asking a very straightforward research question: Is there a relationship between hotspots of lead and hotspots of crime? Furthermore, what is the nature and extent of this relationship? Lastly, is the distribution of lead across communities relative to race, class, and/or ethnicity? To explore these issues, a series of thirteen research hypotheses are derived based on findings from previous lead and crime studies. To test these research hypotheses, data was collected from the city of Chicago's Community Areas (n = 77) in Cook County, Illinois. Information from a range of secondary sources including the U.S. Census, Environmental Protection Agency, Chicago Police Department, and City of Chicago are merged and analyzed. Cross sectional and longitudinal assessments are conducted, and results from a series of negative binomial regressions, fixed effects negative binomial regressions, and correlations are presented. Findings suggest the association between lead and crime appeared particularly robust with respect to rates of violent index crime, but less so for rates of property index crime. Contrary to what prior research suggests, the association between lead and crime appears stronger for rates of arrests for adult index crimes than rates of arrests for juvenile index crime arrests. This study concludes by discussing theory and policy implications alongside recommendations for future study.

The purpose of the present study was to determine the degree of relationship between neurotoxic chemicals in the blood of chemically sensitive patients and psychoneurological functioning. Blood samples were drawn from 30 patients being treated for environmental illness. All patients were administered a standardized intermediate psychoneurological examination. Results indicate a significant positive relationship between psychoneurological (cognitive neurobehavioral) functioning and the number of and total parts per billion of certain environmental toxins (solvents) in the blood of the subjects. The symptoms most commonly exhibited included deficits in short-term memory, problems with coordination and motor sequencing, somatosensory deficits, and cognitive dysfunction.

Delta9-tetrahydrocannabinol (THC) is an active component of marijuana. During recent years, the popularity of marijuana in the United States has increased tremendously. Marijuana edibles are a form of marijuana that has become very popular in recent years. These are easily accessible not only to adolescents but also to young children. According to recent statistical data, the consumption of marijuana edibles by children below the age of 5 has increased 600% in the states that have legalized marijuana. This has led to an adverse impact on children’s health as evidenced by a sudden increase in the number of children seeking emergency assistance in hospitals. In the current research, we addressed the issue of possible persistent effects on children’s behavior due to an earlier exposure to THC. Juvenile rats were treated with 10 mg/kg of THC from postnatal day 10 through 16. Once they reached adolescence, these rats were tested using several behavioral paradigms. To evaluate the biological basis for the behavioral deficits observed, brain samples obtained from these rats were subjected to proteomic analysis to determine any altered pathways related to the behavior. Our behavioral data indicated that juvenile exposure to THC has no effect on anxiety-related behavior in adolescents. However, we observed a significant effect of treatment on multiple parameters related to social interactions. Of these, episodes and time of social play were significantly increased in the THC treated rats suggesting alterations in the reward circuit function occurring as a result of developmental THC exposure. In the proteomics, we observed a significant effect on relevant canonical pathways such as the changes in thrombin and opioid signaling. Thrombin signaling in neurons is associated with processes involved in the connection between neurons and opioid signaling is involved in the activation processes of the reward circuit suggesting that juvenile THC exposure alters these processes in adolescence which could have detrimental effects on behavior. Overall, our data suggest that consumption of edibles by juveniles leads to altered behavioral and biochemical outcomes in adolescence. This may be detrimental in terms of the appropriate acquisition of skills necessary for meeting the challenges in future life.

Billions of pounds of bisphenol A (BPA) are produced annually around the globe for the manufacture of numerous consumer products, including polycarbonate food and water containers, the protective resin linings of food cans, thermal printing paper, and dental fillings. BPA exposure during nervous system development has been associated with learning and behavioral impairments in animal models. The mode of action for these effects is not clearly defined. While BPA is a weak estrogen receptor (ER) agonist, it is also an estrogen-related receptor gamma (ERR��) agonist. ERR�� binds BPA with 100 times greater affinity than ERs. This study was designed to test the hypothesis that exposure to human-relevant BPA concentrations impacts nervous system development and behavior through ERR�� activation. To examine whether BPA behaves more like an ER or ERR�� ligand, two positive control compounds were used throughout the study: 17��-estradiol (E2) and GSK4716, ER and ERR�� agonists, respectively. Initial behavior testing results included the observation that neurodevelopmental exposure to 0.01 or 0.1 ��M BPA led to hyperactivity in larvae, while exposure to 0.1 or 1 ��M BPA led to learning deficits in adult zebrafish. Exposure to 0.1 ��M E2 or GSK4716 also led to larval hyperactivity. To identify early molecular signaling events that lead to the observed neurobehavioral phenotypes, a global gene expression analysis using a 135K zebrafish microarray was conducted. The concentrations of compounds tested were anchored to the common larval hyperactivity phenotype they elicited. Gross abnormalities, in the case of higher concentrations of BPA and E2, were also anchored phenotypes included in the analysis. Functional pathway analysis of the BPA versus E2 results predicted an impact on prothrombin signaling from the two lower concentrations of BPA and E2. Both BPA and GSK4716 were also predicted to impact nervous system development, potentially involving inhibition of the upstream regulator, SIM1. Additionally, GSK4716 exposure was predicted to inhibit neuron migration. There were fewer similarities in transcriptional responses between BPA and E2 when the lower versus higher concentrations were compared, suggesting different mechanisms operated at the higher concentrations. Subsequent experiments were focused on the role of ERR�� in the larval hyperactivity phenotype. Transient ERR�� knockdown by antisense oligonucleotide morpholino during the first 24 hours of development abrogated the hyperactive phenotype induced by 0.1 ��M BPA exposure. Transient ERR�� knockdown during the first 48 hours of development resulted in developmental delays, craniofacial defects, pericardial edema, and severe body axis curvature. This work is the first to identify behavioral effects in a fish from developmental BPA exposure. It is also the first study to confirm a role for ERR�� in mediating BPA's neurobehavioral effects in any animal model. The global gene expression analysis identified similarities between BPA, E2, and GSK4716, suggesting that BPA's mode of action may involve crosstalk between ERR�� and other ERs. These results from human-relevant BPA exposures help explain the widely documented in vivo effects of BPA, despite low binding affinity exhibited by nuclear ERs. ERR�� is an evolutionarily conserved vertebrate receptor and the developmental impacts of BPA in the zebrafish are an indication of hazard potential to vertebrates. They are also an important translational step toward knowing the hazard potential from human developmental exposure to BPA and yet unknown environmental ligands of ERR��. / Graduation date: 2013 / Access restricted to the OSU Community, at author's request, from Dec. 21, 2012 - June 21, 2013