Cerebral cortex, hippocampus, striatum and cerebellum show differential susceptibility to quinolinic acid-induced oxidative stress

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Web End = Neurol Sci (2015) 36:14491456 DOI 10.1007/s10072-015-2180-7

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Web End = Cerebral cortex, hippocampus, striatum and cerebellum show differential susceptibility to quinolinic acid-induced oxidative stress

Samuel Vandresen-Filho1,2 Wagner Carbolin Martins1 Daniela Bohn Bertoldo1

Gianni Mancini1 Andreza Fabro De Bem1 Carla Ins Tasca1

Received: 8 November 2014 / Accepted: 17 March 2015 / Published online: 25 March 2015 Springer-Verlag Italia 2015

Abstract Quinolinic acid (QA) is a NMDA receptor agonist implicated in pathological conditions, such as neurodegenerative diseases and epilepsy. Time-course responses of different brain regions after QA i.c.v. infusion are not known. We aimed to investigate the time-course effects of QA infusion on oxidative stress-related parameters on different brain regions. In cerebral cortex, QA infusion promoted an early (1 h) decrease of NPSH levels and GR activity followed by a later increase in ROS production (8 h) and TBARS detection (2472 h). In the hippocampus, QA promoted an increase in ROS production that lasted 8 h. Striatal tissue presented a later increase in ROS generation (872 h) after QA infusion. In the cerebellum, an increase in the GPx activity after 8 h was the only effect observed. These results show that oxidative stress induced by QA i.c.v. infusion is region and time dependent.

Keywords Quinolinic acid Oxidative stress

Antioxidant enzymes

Introduction

Quinolinic acid (QA) is a NMDA receptor (NMDAR) agonist and sustained activation of NMDAR by QA may cause excitotoxicity through increased intracellular calcium concentration [1]. Increased calcium inux may lead to activation of nitric oxide synthase, disruption of mitochondrial function promoting increased reactive oxygen species (ROS) generation and ATP depletion [2]. QA can modulate glutamate transport as it increases synaptosomal release of glutamate and decreases glutamate uptake by astrocytes in culture and in hippocampal slices [3]. QA also increases the glutamate uptake into synaptic vesicles [4], which may contribute to increased glutamate levels in the synaptic cleft, resulting in excitotoxicity [5]. Given these characteristics, i.c.v. QA infusion is used in models studying the effects of overstimulation of the glutamatergic system and it has contributed to the comprehension...