Function and expression of purinoceptors in white matter astrocytes in situ

点击翻译按钮获取中文摘要

Studies on brain function have by and large focussed on neurons. However, the most numerous cells in the central nervous system (CNS) are astrocytes, but we still know little about their functions. Early concepts envisaged astrocytes as passive and unexcitable structural elements, much like the connective tissues of organs in the periphery. However, it is now clear that astrocytes are dynamic cells and communicate with each other by way of intracellular waves of calcium. In addition, astrocytes communicate with each and with neurons using chemical neurotransmitters. A key role for the neurotransmitter ATP has been proposed as diffusible signal between glia and between glia and neurons. In addition, calcium controls multiple intracellular pathways that regulate the function of astrocytes. Notably, ATP-mediated calcium signalling may have a particular role in pathology. We propose to test to perform a comprehensive investigation of the mechanisms and actions of ATP in astrocyte physiology and pathology. This work meets several priorities identified by the Biochemistry and Cell Biology Committee. Three themes have been outlined by this committee, fundamentals of cell biology, the cell and its environment, and specialised cell function. The proposal is relevant to all three of these themes. Astrocytes are specialised cells with many unresolved functions and this project will address the fundamental biological question of how ATP-mediated signalling mechanisms regulates their function. We will examine the expression and function of signalling pathways, which fits the priority area concerned with the biochemical and functional properties of membrane proteins. The information has an important bearing on basic neurobiology, brain development, and CNS damage and disease states.