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This chapter reviews present knowledge of the possible roles of taurine as a neurotransmitter or neuromodulator. Neurons and glia possess biosynthetic machinery and ample amounts and efficient reuptake of taurine. It is released by depolarization, but the Ca2+ dependency of stimulated release is as yet not definitely settled. Taurine enhances the chloride conductance of plasma membranes in nerve cells and induces hyperpolarization with subsequent inhibition. It remains open whether or not taurine possesses receptors of its own or whether its actions are mediated by GABA and glycine receptors. Taurine may be a neurotransmitter in certain brain areas, more likely in developing animals and in species other than mammals, but no taurinergic nerve tracts are known. Taurine is not a neuromodulator in the classical sense as it has actions of its own in the synaptic region and does not of itself influence the functions of established neurotransmitters. [ABSTRACT FROM AUTHOR]

There is an intimate relationship between ion transport and energy metabolism in the brain. All ion transport is driven directly or indirectly by ATP, and the support of ion homeostasis represents the largest demand on energy production in the brain. Failure of ion homeostasis because of the interruption of energy generation has devastating consequences. This chapter reviews the principal mechanisms responsible for maintaining homeostasis of Na+, K+, and Ca2+, and the mechanisms controlling Zn2+ as an example of trace metal transport. The chapter also discusses the interplay between ion loads and energy production. Finally, we present a description of some of the mechanisms that link pathophysiological states with alterations in ion transport and energy metabolism. [ABSTRACT FROM AUTHOR]

Control of glucocorticoid secretion is essential for the health and survival of all vertebrate organisms. Hyper- and hypo-secretion of glucocorticoids are associated with disease processes, underlying the importance of maintaining normal daily glucocorticoid rhythms and generating appropriate glucocorticoid responses to stress. This chapter reviews the principle neurochemical mechanisms that operate in the CNS to regulate excitation and inhibition of the hypothalam-pituitary-adrenocortical (HPA) axis. Daily glucocorticoid secretion is controlled by monoamine and GABAergic circuitry, likely relayed through the suprachiasmatic nucleus. Glucocorticoids appear to play a role in circadian inhibition, exerted via the mineralocorticoid receptor. Neurochemical activation of the HPA axis is highly dependent on modality and intensity. Notably, brainstem norepinephrine/epinephrine neurons are selectively involved in HPA axis activation by systemic stressors. Activation of the HPA axis by psychogenic stressors is intensity-dependent, with peptidergic (vasopressin, Orphanin FQ) and glutamatergic systems playing a role in responses to mild, but not intense stressors. Responses to intense psychogenic stressors appear to involve serotonergic and peptidergic systems (e.g., brainstem glucagon-like peptide 1). Inhibition of the HPA axis is accomplished by GABAergic signals and glucocorticoid feedback, the latter of which is controlled by combined actions at glucocorticoid and mineralocorticoid receptors. The neurochemical systems underlying chronic stress-induced changes in HPA function remain to be elucidated. Overall, the data to date identify numerous candidate neurochemical systems capable of modulating HPA axis activity. Selective targeting of these systems may prove useful for treatment of HPA axis-related disease states. [ABSTRACT FROM AUTHOR]

Neurons are highly integrated both anatomically and metabolically with glial cells, and thus glial cells have a major influence on neuronal survival in ischemia and excitotoxicity. Of the three types of glia in the central nervous system–astrocytes, oligodendrocytes, and microglia–the role of astrocytes in excitotoxicity and ischemia has been best characterized. Under different settings, astrocytes can both limit or contribute to excitotoxic neuronal death. Astrocytes also influence oxidative neuronal injury and contribute to neuronal demise through secretion of nitric oxide and cytokines. Microglia, the resident macrophages of the CNS, can also have both deleterious and salutary effects on neuronal survival. Activated microglia can kill neurons, but on the other hand normal microglial function is probably required for brain remodeling after injury. Interactions between microglia and astrocytes engender an additional layer of complexity to these post–ischemic processes. [ABSTRACT FROM AUTHOR]

This chapter reviews the occurrence, distribution, metabolism, transport, and actions of the simple sulphur-containing nonproteinaceous amino acid taurine. It is a ubiquitous constituent of virtually all animal cells, particularly enriched in the electrically excitable cells of the nervous system, retina, heart, and muscles. Taurine is present in both neuronal and glial cells, exhibiting moderate regional and cellular variations. It is partly synthesized in situ, but the main supply to the central nervous system (CNS) is from blood plasma. Taurine is taken up by the brain via a saturable transporter and penetrates cells requiring Na+ and Cl−. The release is fomented by cell swelling, depolarizing stimuli, and various cell-damaging conditions. Taurine interferes with both GABAA and glycine receptors, depending on their subunit composition and amino acid structure. It also affects GABAB receptors, at least in specific structures. The existence of specific taurine receptors and the function of taurine as a neurotransmitter await further investigation. A number of taurine derivatives have been synthesized and tested for their efficacy in counteracting seizures, ameliorating ischemia-induced damage, and protecting neural cells from the toxic actions of xenobiotics. This is an area of research, which may produce new drugs and therapeutic strategies in the future. [ABSTRACT FROM AUTHOR]