This project examined functional changes in neuronal and glial cells and the subsequent interaction and signalling between these cells in the nervous system following perturbation. Although various responses of neural cells exist, this work has focused on two aspects, 1) the ability of the cell to maintain calcium homeostasis which plays a critical regulatory role in cell-cell communication and signalling. A disruption in intracellular calcium can disrupt the calcium-mediated signal transduction processes resulting in a cascade of intracellular effects including alterations in transcription factors and specific mRNAs for cellular proteins. 2) the response of microglia and astrocytes to neural injury and the role for pro-inflammation cytokines, IL-1, IL-6, TNA- alpha, as signalling mechanisms in the cascade of neurotoxicity. Within the nervous system cytokines are thought to have active roles in the pathophysiological changes seen in various neurological diseases and trauma. Early responses to chemical injury suggest a possible involvement of pro-inflammatory cytokines in the signalling process to initiate the injury response cascade of neuronal necrosis, astrogliosis, and subsequent neuronal loss. The interaction between neurons and glia will be investigated by examining the signalling mechanism of cytokines on neuronal cells with regard to calcium homeostasis and gap-junctional communication.
