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The size, dendritic geometry, and electrophysiological properties of neurones are regulated by interactions with their targets. In the case of sympathetic neurones, the target-dependent alterations in neuronal morphology and properties can be reproduced by manipulating the target-derived neurotrophic factor, NGF. Thus, the target-dependence of the neuronal state consists in its dependence on the target-derived neurotrophic factor. Besides the cell properties, neuronal survival itself depends on the target or the target-derived neurotrophic factor. The target-dependence of neuronal survival commences approximately when the neurone forms connections with its target, presumably along with the synthesis of the trophic factor in the target tissue and the expression of its receptors in the neurone.

As Gutmann (1976) predicted, the analysis of neurotrophic mechanisms is easier if the nature of the trophic factor is known. Fortunately, several neurotrophic factors have been now identifed. This chapter begins with the features of these identifed neurotrophic factors. Although each neurotrophic factor affects many phenotypes, it first focuses on the most evident phenotype, cell survival. The chapter aims to characterize the influence of identified neurotrophic factors, using cell survival as a criterion. As is seen, these neurotrophic factors can rescue different neurones from cell death. The deprivation of some of these neurotrophic factors causes the neurones to deviate from the normal embryonic programme, resulting in cell death.

Cytokine is the term used to describe a large and expanding group or family of polypeptides which can be synthesized by most cell types, and influence numerous biological processes. Recent research indicates that cytokines have diverse effects on nervous system function and have been implicated in various forms of neurological disease and injury. However, the emerging picture is a complex one, and cytokines have been proposed as both mediators and inhibitors of neuronal survival and death. Some of this complexity arises from the varied experimental approaches employed, the absence of suitable inhibitors or receptor antagonists for many cytokines, and the wide range of doses, concentrations, bioactivity and origin of the cytokines used. In order to establish a biological role for any cytokine in neurodegeneration, it is necessary to demonstrate its synthesis in an appropriate temporal and spatial manner, the effects of the cytokine at relevant concentrations, and that inhibition of its action modifies neurodegeneration. This chapter reviews the methods which have been used and are now becoming available to achieve these aims. It summarizes known mechanisms of neurodegeneration in order to facilitate discussion of possible sites of cytokine action.

In several brain regions, N-methyl-d-aspartate (NMDA) receptors are specially effective during the developmental period, where they appear to play important roles in the formation and stabilization of developing synapses. The early activation of NMDA receptors could also provide signals which promote neuronal survival, growth, and differentiation. This chapter attempts to review this area of NMDA receptor research and to place the information into a chronological framework.