Abstract

Unilateral injection of colchicine into the dentate gyrus, kainic acid into the CA3 pyramidal cell field, or cerebrospinal fluid into either site produced significant increases in ornithine decarboxylase (ODC) activity in both the injected and noninjected hippocampi. The magnitude as well as the time course of these changes varied with the cytotoxin, the site of injection, and whether or not animals bad been pretreated with ganglioside GM1. The ganglioside regimen reduced the ODC response in the injected hippocampus but increased it on the side contralateral to the colchicine injection. In contrast, GM1 enhanced the ODC response produced by kainic acid in the injected but not the unin-jected hippocampus. In a subsequent study morphometric analysis of the hippocampus revealed that pretreatment with GM1 did not alter the extent of hippocampal injury induced by either cytotoxin. These data indicate that the changes in ODC activity observed following hippocampal damage represent a complex set of biochemical changes that might serve to protect primary or secondary sites of insult and/or to promote either adaptive or maladaptive neural reorganization. Ganglioside GM1 altered the ODC response without minimizing the histopathological changes induced by the cytotoxins. The role of polyamines in neural, behavioral, and synaptic plasticity is currently under study.

Highlights

  • Ornithine decarboxylase (ODC) is the rate-limiting enzyme in the biosynthesis of the polyamines putrescine, spermine, and spermidine [4, 9, 33]

  • There is evidence that changes in ODC activity reflect maturational processes occurring in the developing nervous system [31]

  • cerebrospinal fluid (CSF) injected into either of the hippocampal sites produced increases in ODC activity which were smaller and more transient in nature than those produced by the cytotoxins

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Summary

Introduction

Ornithine decarboxylase (ODC) is the rate-limiting enzyme in the biosynthesis of the polyamines putrescine, spermine, and spermidine [4, 9, 33]. This enzyme is widely distributed in many types of mammalian tissue and is prevalent in rapidly growing tissue such as neoplasia and in embryos. There is evidence that changes in ODC activity reflect maturational processes occurring in the developing nervous system [31]. The activity of this enzyme can be modulated by a variety of extrinsic factors. On the basis of these observations, it has been postulated that alterations in ODC activity reflect an involvement of polyamines in growth and differentiation of cells and in their response to injury [19, 30, 33]

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