• Neuroscience · Jul 2018

    Sustained Activation of JNK Induced by Quinolinic Acid Alters the BDNF/TrkB Axis in the Rat Striatum.

    • Ricardo A Santana-Martínez, Juan Carlos León-Contreras, Diana Barrera-Oviedo, José Pedraza-Chaverri, Rogelio Hernández-Pando, and Perla D Maldonado.
    • Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, CDMX 14269, Mexico.
    • Neuroscience. 2018 Jul 15; 383: 22-32.

    AbstractOxidative stress secondary to excitotoxicity is a common factor in the physiopathology of a variety of neurological disorders. In response to oxidative stress, several signaling pathways, such as MAPK, are activated or inactivated. Mitogen-activated protein kinase (MAPK) family activation must be finely regulated in time and intensity, as this pathway may either preserve cell survival or promote cell death. In the present study, the activation of MAPK in the excitotoxic injury induced by quinolinic acid (QUIN) was examined in vivo, at short and long times. We used different doses (30, 60, 120 and 240 nmol) of QUIN injected intrastriatally in the right rat striatum and the effect of this treatment on motor deficits, cellular damage, MAPK activation and BDNF/TrkB axis, were evaluated at 2 h and 7 days post-lesion. Higher doses of QUIN (120 and 240 nmol) induced rat motor deficits and caused morphological changes in neurons around the lesion core. QUIN decreased the activation of ERK1/2 in a dose-dependent manner at 7 days post-injection, and induced a sustained increase of c-Jun NH2-terminal kinase (JNK) activation from 2 h to 7 days post-injury. JNK activation was dependent on the QUIN-induced NMDAr activation (only 120 nmol). No significant difference in p38 activation with QUIN was observed. QUIN (120 and 240 nmol) decreased BDNF/TrkB levels at 7 days post-injury. JNK inhibition (by an intracerebroventricular injection of SP600125) prevented the QUIN-induced reduction in BDNF and TrkB at 7 day post-injury, suggesting a role for the QUIN-induced JNK activation on the observed decrease in BDNF levels.Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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