[Truncated abstract] Lead is an environmental persistent pollutant with potent neurotoxic effects. In vitro and in vivo studies have reported that lead induces neuronal death, astrocyte activation, cognitive deficits, as well as learning and memory impairments. Involvement of the immune system and inflammation has also been reported in lead toxicity. In humans, lead concentrations are difficult to measure and assess, especially for the brain. However, 10 μM of lead is expected to be the highest concentration that is reached in the central nervous system (CNS). Australia is one of the main lead mining and processing countries with reported lead toxicity in cities close to the mining sites and ports. Microglia are the resident innate immune cells of the brain. As the macrophages of the CNS, microglia share common characteristics with the monocyte-macrophage lineage such as expression of particular surface markers and chemokine/cytokine receptors, antigen presentation and phagocytic activity. Microglia activation in response to lead exposure has been reported in animal studies. This activation is usually followed by secretion of pro-inflammatory cytokines and chemokines as mediators of the innate immunity. In the CNS, chemokines and their receptors are important in the neuron-microglia interaction, as well as during CNS development by mediating neurogenesis, migration and differentiation of neuronal progenitor cells. Despite being the innate immune effectors of the CNS, the role of human microglia in lead-induced toxicity and inflammation is still unknown. Furthermore, at the commencement of this study, there was no standardized simple model available to investigate the biology of human microglia. To investigate the effects of lead on human microglia, first, a new human in vitro microglia model (M-MG) using blood-derived monocyte was developed and established (Samar Etemad et al., Journal of Neuroscience Methods 2012, 30, 79-89). In the next step, the effects of lead exposure on human microglia, were studied to examine in different aspects such as morphology, phenotype and function. In addition, the human microglia cell line HMC3 and human neuronal precursors cell line HCN2 were used as established human microglia and neuronal precursor cell lines in this study...
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2013|