Efeitos da espermina sobre parâmetros motores, cognitivos e neuromorfológicos em um modelo experimental da doença de huntington

Abstract

Spermine (SPM) is an aliphatic amine which contains four nucleophilic centers and is found in all eukaryotic cells, including nervous cells. It belongs to the group of polyamines, which are molecules associated with both neuroprotection and neurotoxicity. The aim of this study was to investigate the effects of spermine on some parameters of toxicity induced by striatal administration of quinolinic acid (QA), an experimental model of Huntington s disease in adult and male Wistar rats. The intrastriatal administration of QA (180 nmol/site) induced contralateral rotations and increase the number of contralateral body swings. The previous striatal administration of SPM caused mixed effects: at the dose of 0.1 nmol/site increased the number of contralateral rotations; but at 10 nmol/site it reduced both the number of rotations and the contralateral body swings induced by QA. The mechanism by which SPM decreases these motor alterations is probably through its interaction with the NMDA receptor, since the co-administration with arcaine (antagonist of polyamine binding sites on this receptor) reversed its protective effect. The increase of protein carbonyl content induced by QA (180 nmol/site) in striatum of rats was prevented by the administration of 10 nmol/site of SPM. Besides, the bilateral striatal injection of QA (180 nmol/site) impaired the performance in the recognition memory task. The post-training striatal administration of SPM (0.1 and 1 nmol/site) reversed the QA-induced cognitive deficit. It was also evaluated whether spermine prevented QA-induced neuromorphological alterations. QA caused striatal neuronal degeneration and reactive astrogliosis. SPM, at the dose that improved the cognitive performance (0.1 nmol/site), had no effect on striatal neuronal degeneration but reversed the intense astrocytic reaction induced by QA. These results suggest that SPM has neuroprotective properties, presenting a dose dependent pattern of polyamine, in this experimental model of Huntington disease.