A neuroprotective role for polyamines in a Xenopus tadpole model of epilepsy

Abstract

Polyamines are endogenous molecules involved in cell damage following neurological insults, although it is unclear whether polyamines reduce or exacerbate this damage. We used a developmental seizure model in which we exposed Xenopus laevis tadpoles to pentylenetetrazole (PTZ), a known convulsant. We found that, after an initial PTZ exposure, seizure onset times were delayed in response to a second PTZ exposure 4 h later. This protective effect was a result of activity-dependent increases in synthesis of putrescine, the simplest polyamine. Unlike more complex polyamines that directly modulate ion channels, putrescine exerted its effect by altering the balance of excitation to inhibition. Tectal neuron recordings, 4 h after the initial seizure, revealed an elevated frequency of GABAergic spontaneous inhibitory postsynaptic currents. Our data suggest that this effect is mediated by an atypical pathway that converts putrescine into GABA, which then activates presynaptic GABA(B) receptors. Our data suggest that polyamines have a previously unknown neuroprotective role in the developing brain.