Dietrich Van Calker,     Max-Planck-Institut für Biochemie, Martinsried, Federal Republic of Germany

Bernd Hamprecht,     Physiologisch–Chemisches Institut, Universität Wüzburg, Würzburg, Federal Republic of Germany

Publisher Summary

This chapter focusses on the effects of neurohormones on glial cells. The receptors for several putative neurohormones are expressed by transformed glial cells and by immature glial cells from rodent brain. The two most enigmatic fields of neuroscience, namely, the glial function and the problem of learning and memory, have been combined in the speculation that interactions between neurons and glial cells may be the basis of the higher adaptive functions of the brain. The glial cells and neurons not only exchange trophic or mitotic factors but also integrate their information-processing capacity by the exchange of hormonal signals. Both anatomical and physiological evidence suggests that, in addition to their role as neurotransmitters, biogenic amines might also act as neuromodulators or neurohormones, a mode of operation intermediate between the private addressing of classical synaptic messengers and the broadcasting of neuroendocrine secretion. The problem of obtaining mature glial cells of sufficient purity and integrity from adult brain is still unsolved. Most studies are performed using cultured glial cells, either permanent cell lines derived from tumors or primary cultures from perinatal rodent brain enriched in glia-like cells. The chapter briefly discusses the question of the reliability of these cells as models for neuroglia.

I Introduction

The enormous effort being made to understand the functions of neuroglia may be judged from the increasing number of monographs, anthologies, and reviews dealing with the subject (Glees, 1955; Windle, 1958; Nakai, 1963; Galambos, 1964; De Robertis and Carrea, 1965; Kuffler and Nicholls, 1966, 1977; Bunge, 1968; Lasansky, 1971; Fleischhauer, 1972; Johnston and Roots, 1972; de Vellis and Kukes, 1973; Watson, 1974; Privat, 1975; Somjen, 1975; Fedoroff and Hertz, 1978; Schoffeniels et al., 1978; Varon and Somjen, 1979). Nevertheless, our knowledge of what might be the biochemical function of glial cells is still very limited. The two most enigmatic fields of neuroscience, glial function and the problem of learning and memory, have been combined in the speculation that interactions between neurons and glial cells may be the basis of the “higher” adaptive functions of the brain (Galambos, 1961, 1964; Svaetichin et al., 1965; Roitbak, 1970). A prerequisite for this idea is that glial cells and neurons not only exchange trophic or mitotic factors (for a review of this subject, see Varon and Bunge, 1978) but also integrate their information-processing capacity by the exchange of hormonal signals. The question as to whether glial cells possess receptors for such signals is the subject of this review. Such signaling compounds neither fit into the definition of a “hormone” (which is released into the circulation) nor represent a classic “neurotransmitter” (which is released by the presynaptic terminal and acts at the membranes facing the synaptic cleft, the pre- and postsynaptic membranes). Indeed, both anatomical and physiological evidence suggests that, in addition to their role as neurotransmitters, biogenic amines might also act as “neuromodulators” or “neurohormones,” “a mode of operation intermediate between the private addressing of classical synaptic messengers and the broadcasting of neuroendocrine secretion” (Dismukes, 1977; see also Henn, 1978). A similar role may be assessed to the newly discovered “peptidergic” systems in the brain (Scharrer, 1978). In this article the term “neurohormone” is used to designate compounds that have been shown to or are suspected of, transmitting information across the extracellular space, classic hormones and neurotransmitters as well as agents not yet classified. However, we shall not discuss factors, the only known functions of which are to supply growth-promoting, trophic, mitotic, or “differentiating” influences. These have been comprehensively reviewed by others (Westermark and Wasteson, 1975; Lim et al., 1978; Varon and Bunge, 1978).

II Models for Glial Cells

The problem of obtaining mature glial cells of sufficient purity and integrity from adult brain is still unsolved, although some progress has been made recently (see Henn, this volume). Most studies, therefore, were performed using cultured glial cells, either permanent cell lines derived from tumors or primary cultures from perinatal rodent brain enriched in glia-like cells. This section briefly discusses the question of the reliability of these cells as models for neuroglia.