An in-silico model of the biosynthesis of neurotransmitter glutamate, elucidates the complex regulatory role of glucocorticoids in neurotransmitter glutamate release

An in-silico model, of the glucocorticoid regulated glutamate release, in rat hippocampal tissue, is constructed. The model permits the pseudo-steady state estimation of various fluxes, experimentally impossible to measure, from a set of measured rates. Estimates of the astrocytic pyruvate carboxylase reaction and the neuronal TCA cycle rates are correlated with different dexamethasone concentrations, in order to extrapolate explicit kinetic equations. The model Suggests that the observed effects of glucocorticoids can be attributed to the inhibitory actions of dexamethasone on two competing pathways, that of the neuronal TCA cycle and the biosynthetic pathway of neurotransmitter glutamate. (C) 2009 Elsevier Ltd. All rights reserved.