Astrocytes perform important and varied roles in the brain. The location of these glial cells in and around neurons, and their close contact via specialized 'end-feet' with the cerebral vasculature, implicates astrocytes in bi-directional signalling processes. The realization that astrocytes secrete a number of neuroactive amino acids and peptides, together with vasoactive prostanoids and nitrosyl compounds, reinforces this proposition. The long term objective of this research is to study such proposed roles for astrocytes in patho-physiological CNS function; in particular, to determine the significance of their demonstrated ability to synthesize and release a labile, non-prostanoid vasodilator with properties similar to nitric oxide. Well-characteized astroglial cell cultures derived from the neonatal rat forebrain will be used to: 1. Investigate the regulation and control of the enzyme (nitric oxide synthase) predicted to be responsible for the synthesis of the astrocyte-derived relaxing factor. 2. Isolate and purify the enzyme in order to define, and so compare, its biochemical properties with similar enzymes expressed in other cell types of neural and extra-neural origin. This investigation will (a) reveal how synthesis of nitrosyl compounds and their release from astrocytes are regulated, (b) suggest probable interactions between astrocytes, neurons and cells of the vasculature, and (c) lead to predictions about the involvement of astroglial cells in pathologies concerning the cerebral vasculature which can then be experimentally verified.
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