Antioxidative effect of nerve growth factor (NGF) in rat thalamus after quinolinic acid-induced neurotoxicity

Abstract

Quinolinic acid (QA) produces a pattern of selective cell loss in the striatum, that closely mimics that of Huntington's disease (HD). The aim of this study was to investigate the antioxidative status in the thalamus after intrastriatal application of QA and the influence of nerve growth factor (NGF) on such neurotoxicity. Wistar rats were treated intrastriatally (coordinates: 8.4A, 2.6L, 4.8V), using a stereotaxic instrument. The first group was treated with QA (150 nmol/l). The second group was treated with QA, followed by NGF (4.5 mg/kg b.w). The control group was treated with 0.9 % saline solution. Seven days after the treatment, we found decreased superoxide dismutase (SOD) activity in mitochondrial fractions of the striatum of both groups. In the thalamus, SOD activity showed no differences. The content of superoxide anion increased in the striatum of QA- treated animals. It was decreased in both structures in the group that was treated with QA and NGF. In the QA+ NGF-treated group, we found increased glutathione peroxidase (GSHPx) and GSH, compared to the group that was treated with QA only, but these values were lower than in the controls. Thus, NGF showed beneficial effects on the oxido-reduction status in the striatum, and also in the thalamus, a structure that is separated from but tightly connected with the striatum.

Hinolinska kiselina (HK) prouzrokuje takav selektivni gubitak ćelija u strijatumu, koji veoma dobro imitira onaj kod Huntingtonove bolesti. Cilj ovog istraživanja bio je da se ispita antioksidativni status u talamusu nakon aplikacije HK u strijatum i uticaj NGF na takvu neurotoksičnost. Wistar pacovi su tretirani intrastrijatno, pomoću stereotaksičnog instrumenta (koordinate: 8,4A, 2,6L, 4,8V). Prva grupa je bila tretirana HK (150 nmol/l). Druga grupa je bila tretirana HK, a nakon toga je dobila NGF (4.5 mg/ kg b.w). Kontrolna grupa je bila tretirana fiziološkim rastvorom. Sedam dana nakon tretmana, u mitohondrijskim frakcijama strijatuma, našli smo smanjenu aktivnost SOD u obema grupama. U talamusu, aktivnost SOD se nije promenila. Sadržaj superoksidnog anjona se povećao u strijatumu životinja koje su bile tretirane HK, a smanjio se u obema strukturama, u grupi koja je bila tretirana sa HK i NGF. U HK+ NGF-tretiranoj grupi, našli smo povećanu aktivnost GSHPx i GSH u odnosu na grupu koja je bila tretirana samo sa HK, ali su te vrednosti bile manje u odnosu na kontrolne. NGF je pokazao povoljne efekte na oksido-reduktivni status u strijatumu, ali takođe i u talamusu, strukturi koja je odvojena, ali veoma blisko povezana sa strijatumom.