Transgenic animals as models in the study of the neurobiological role of polyamines

Natural polyamines, putrescine, spermidine and spermine, exhibit a number of neurophysiological and metabolic effects in brain preparations. In the in vitro studies, several specific sites of action have been identified such as ion channels, transmitter release and Ca2+ homeostasis. Polyamines have been linked to the development of neuronal degeneration caused by, for instance, epileptic seizures and stroke. The role of endogenous polyamines in the functioning brain is not clear, however. We review the work carried out using state-of-the-art transgenic animal models for polyamine research. A number of transgenic mouse lines carrying human ornithine decarboxylase, spermidine synthase and S-adenosylmethionine decarboxylase gene have been generated. Of these animals those with ornithine decarboxylase transgene show an extensive and constitutive expression of the enzyme in the brain with an exceedingly high putrescine concentration, a phenotype that is not encountered under physiological conditions. In this article we review the neurometabolic, behavioural and histological data that has been obtained from these transgenic mice.