The rationale for the localization of polyamine pathway enzymes in the brain

Abstract

Polyamines, including spermidine, spermine, and agmatine, serve several brain-specific functions. Polyamine transport mechanisms may account for the redistribution of these organic cations, which may also be synaptically released as neuromodulators or neurotransmitters, in the brain. Therefore, the localization of polyamine pathway enzymes, in addition to the localization and functional investigation of the polyamines itself, provides valuable insights regarding the identification of cell- and region-specific roles for polyamines, notably in the context of mental disorders and neurodegenerative diseases. Identified neuronal circuits are subject to physiological and pharmacological investigations. With this respect, we electrophysiologically studied the cerebellar cortex and the medial habenula, showing a prominent synaptic expression of spermidine synthase and agmatinase, respectively. In both areas, the relevant polyamines clearly influence the electrical activity. The medial habenula may be involved with the aetiology of major depressive disorder. In this context, the expression of agmatinase in other brain areas, e.g. the paraventricular thalamic nucleus, possibly also involved with depression, is discussed.