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Jonsson G, Pollare T, Hallman H, Sachs C.
“Developmental Plasticity Of Central Serotonin Neurons After 5,7-dihydroxytryptamine Treatment”.
Ann. NY Acad. Sci.. 1978;305:328-345.
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Abstract
It is well known that the response to injury of the immature or developing nervous system and the mature nervous system is different in at least two ways. On the one hand there is experimental evidence that the infant brain is more vulnerable than is the adult brain after certain damaging-treatments. On the other hand, it has frequently been observed in various types of brain lesion experiments that there is more sparing or a greater extent of functional recovery when operations are performed in infants than in adults (see Reference I ). The latter findings have often been ascribed to the fact that the developing brain possesses a greater potential for neuronal regeneration and/or reorganization. Despite extensive studies, this contention is still open to debate. With this controversy in mind. we have focused our attention on an attempt to determine how the central catecholamine and 5-hydroxytryptamine (5-HT) neurons in the rat respond to early damage induced by the monoamine neurotoxins 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (5,7-HT);. The neurotoxin-induced effects have mainly been analyzed by means of histochemical and neurochemical techniques. In these studies, we elected to administer the neurotoxins systemically in the neonatal stage, when the blood-brain barrier is not yet fully developed, allowing the neurotoxin to enter the brain, where it can elicit its neurodegenerative action on monoamine neurons. This route of neurotoxin administration is advantageous with respect to specificity, as compared to, for example, intracisternal or local intracerebral injections; also, few nonspecific cytotoxic effects have yet been observed after systemic injection. Since the monoamine neurotoxins are generally cytotoxic and the specificity of the neurodegenerative action is solely dependent on their selective accumulation within monoamine neurons, it is essential to avoid injection of high concentrations of neurotoxin locally to obtain a high degree of specificity in terms of neurotoxic effect. The latter requirement may be difficult to satisfy by intracisternal or intracerebral injection. A disadvantage with the systemic route of administration is that it may lead to rather heterogeneous effects with respect to extent of denervation of the various monoamine nerve terminal projections and thus to defining the damage exactly from a neuroanatomic standpoint, which is of greatest importance for an adequate interpretation of the effects observed after neurotoxin administration: Preliminary studies of the effect of neonatal administration of the monoamine neurotoxins revealed that the immature monoamine neurons in the brain reacted in a rather complex manner, with marked regional differences. and quite differently from the response in adult animals. In this paper. we will review our studies on the altered development of central 5-HT neurons induced by 5,7-HT. with special reference to characterization of the changes, determination of the specificity of action of 5,7-HT, and the mechanisms involved in altered ontogenetic development.
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