Neurotoxic effects of the intrastriatal injection of spermine and spermidine: lack of involvement of NMDA receptors

Abstract

The injection into the rat striatum of the polyamines spermine and spermidine (30–300 nmol) produced, 1 week after injection, a dose related loss of the neuronal markers glutamate decarboxylase and choline acetyltransferase and a decrease in the density of N- methyl- d-aspartate (NMDA) receptors (as labelled with [ 3H]TCP). In parallel, an increase in peripheral type benzodiazepine ( p) binding site density (a marker of the associated glial reaction and macrophage invasion) was observed. Intrastriatal injection of putrescine (300 nmol) did not significantly alter any of these markers. The effect of spermine on these neuronal and glial markers was maximal 3 days after injection, and tended towards control levels at 16 days post injection. The neurotoxic effects of spermine were confirmed by histological analysis demonstrating a massive neuronal loss around the injection site and an accumulation of astrocytes and phagocytes. The neurotoxic effects of spermine (250 nmol) were not antagonised by the previous administration of the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.). Thus polyamine neurotoxicity in vivo does not seem to involve NMDA receptor activation, although it may possibly be related to the multiple effects of these compounds on diverse calcium channels and processes regulating calcium homoeostasis.