List of ContributorsPrefaceSection 1. Cell Differentiation and Interaction Specializations of Nonneuronal Cell Membranes in the Vertebrate Nervous System I. Introduction II. Gap Junctions III. Tight Junctions IV. Assemblies References Effects of Neurohormones on Glial Cells I. Introduction II. Models for dial Cells III. Receptors for Putative Neurohormones IV. Events Secondary to Receptor Activation V. Conclusions References Retrograde Axonal Transport I. Introduction II. Mechanism of Retrograde Axonal Transport III. Retrograde Transport of Materials Endogenous to the Neuron IV. Retrograde Transport of Materials Exogenous to the Neuron V. Functions of Retrograde Transport of Exogenous Materials VI. Conclusion References Biochemical Characteristics of Individual Neurons I. Introduction II. Single-Cell Samples III. Cell Structure IV. Biochemical Components V. Conclusion ReferencesSection 2. Aging and Pathology Cerebellar Granule Cells in Normal and Neurological Mutants of Mice I. Introduction II. Possible Effect of Purkinje Cells on Proliferation of Granule Cells III. Effect of dial Cells on Granule Cell Migration IV. Survival of Granule Cells in Mutant Mice (Staggerer and Weaver) V. Parallel Fiber-Purkinje Cell Synapses VI. Granule Cell Transmitter VII. Comments on the Use of Neurological Mutants as Model Systems References Cell Generation and Aging of Nontransformed Glial Cells from Adult Humans I. Cell Generation and Aging II. Origin of Adult Human Glia-Like Cell Lines III. Theories about Cellular Aging IV. Basic Characteristics of Adult Human Glia-Like Cells In Vitro V. Relation between Cell Generation and Aging in Human Glia-Like Cells VI. Miniclone Analysis of Glia-Like Cells VII. Conclusions References Age-related Changes in Neuronal and Glial Enzyme Activities I. General Introduction II. Neuron-Specific Enzymes III. Glia-Specific Enzymes IV. Enzymes Associated with Specific Cellular Processes References Glial Fibrillary Acidic (GFA) Protein in Normal Neural Cells and in Pathological Conditions I. Introduction II. Biochemical Properties of GFA Protein III. Preparation of Antisera IV. Immunohistochemical Localization of GFA Protein in Adult CNS V. Gliogenesis VI. Astroglial Response to Injury VII. Astroglial Marker in Vitro VIII. Diagnosis of Brain Tumors ReferencesSection 3. Methodologies In Vitro Behavior of Isolated Oligodendrocytes I. Introduction II. Isolation of Oligodendrocytes III. Oligodendrocyte Subpopulations IV. Culture of Oligodendrocytes V. Conclusions References Biochemical Mapping of Specific Neuronal Pathways I. Introduction II. Techniques for Biochemical Classification of Neurons III. Identification of Interconnections between Neurons Using Different Transmitters References Separation of Neuronal and Glial Cells and Subcellular Constituents I. Introduction II. Methods of Cell Isolation III. Subcellular CNS Fractions IV. New Isolation Techniques V. The Use of Cell Fractions References Separation of Neurons and Glial Cells by Affinity Methods I. Introduction II. Techniques of Separation by Affinity Systems III. Ligands for Neural Cell Surfaces IV. Concluding Remarks ReferencesSubject Index
Effects of Neurohormones on Glial Cells1
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
II Models for Glial Cells
A Clonal Glial Cell Lines
B Primary Cultures from Perinatal Brain Tissue
III Receptors for Putative Neurohormones
A Norepinephrine
B Dopamine
C Histamine
D Prostaglandins
E Acetylcholine
F Adenosine
G Peptides
H Serotonin
I Benzodiazepine
IV Events Secondary to Receptor Activation
A Enzyme Activities
B Interactions with Glucocorticoids
C Morphological Effects
D Refractoriness
E Factors Produced by Glial Cells
V Conclusions
References
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.
A Clonal Glial Cell Lines
Since glial cell lines have recently been reviewed (Pfeiffer et al., 1978), only some brief remarks are given to provide background. By far the most widely studied glial cell line is the rat glioma line C6, which was cloned from a N-nitrosomethylurea-induced brain tumor (Benda et al., 1968, 1971) of Wistar–Furth strain rats (P. Benda, personal communication). Although often referred to as “astrocytoma” cells, C6 cells display markers of oligodendroglia such as 2′, 3′-cyclic-AMP phosphohydrolase (Zanetta et al., 1972; Volpe et al., 1975) and inducibility by hydrocortisone or glycerolphosphate dehydrogenase (GPDH) (Davidson and Benda, 1970; de Vellis et al., 1971, 1977; de Vellis and Brooker, 1973), as well as markers of astrocytes such as the glial fibrillary acidic (GFA) protein (Bissell et al., 1975). C6 cells also contain S-100 protein, another putative glial marker (Benda et al., 1968, 1971). For recent reviews on glial markers see Varon (1978), Varon and Somjen (1979), and Laerum et al. (1978). Of the numerous other glial lines that have been developed (Pfeiffer et al., 1978) only human astrocytoma cells were investigated in some detail as far as receptors for neurohormones were concerned. 138MG cells (Pontén and Macintyre, 1968) were derived from a grade III astrocytoma–glioblastoma. These cells contain S-100 and GFA proteins (Edström et al., 1973; Walum, 1975). 1181N1 cells (Perkins et al., 1971) and 1321N1 cells (a subclone of 1181N1, see Clark et al., 1974) are clonal cell lines derived from 118MG cells which originated from human glioblastoma multiforme (Pontén and Macintyre, 1968). EH-118MG cells were developed through the action of the Engelbreth–Holm strain of Rous sarcoma virus on 118MG cells (Pontén and Macintyre, 1968; Macintyre et al., 1969). It is possible that the combinations of markers or functions expressed in the various clonal glial strains reflect the potentialities of glial cells, but that they are not identical with those of any kind of glial cell in the nervous...
