Premium
NR1 and GluR2 expression mediates excitotoxicity in chronic hypobaric hypoxia
Author(s) -
Hota Sunil K.,
Barhwal Kalpana,
Singh Shashi. B.,
Sairam M.,
Ilavazhagan Govindasamy
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21554
Subject(s) - excitotoxicity , glutamate receptor , nmda receptor , ionotropic effect , pharmacology , hypoxia (environmental) , biology , neurodegeneration , glutamatergic , receptor , kainate receptor , neuroprotection , endocrinology , neuroscience , chemistry , medicine , ampa receptor , biochemistry , disease , organic chemistry , oxygen
Abstract Hypobaric hypoxia has been reported to cause memory dysfunction. The possible molecular mechanism involved, however, remains to be explored. The role that glutamate and its receptors play in causing excitotoxicity in ischemia and neurodegenerative diseases indicates the possible occurrence of a similar phenomenon in hypobaric hypoxia. The present study aimed to elucidate the molecular events occurring at glutamatergic synapses in hypobaric hypoxia using Sprague‐Dawley rats as a model system. The animals were exposed to an altitude of 7,600 m for different durations. Hypobaric hypoxia was found to cause oxidative stress, chromatin condensation, and neurodegeneration. A temporal change in the expression of the ionotropic receptors of glutamate was also observed. Expression of the N ‐methyl‐ D ‐aspartate (NMDA) receptor increased, and expression of glutamate receptor subunit 2 of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionate receptor decreased. We also observed increased activity of glutamate dehydrogenase, indicating greater synthesis and release of glutamate after 3 and 7 days of exposure. Administration of a selective NMDA antagonist during exposure was found to ameliorate neuronal degeneration, providing evidence for the occurrence of excitotoxicity in hypobaric hypoxia. Our study indicates that excitotoxicity occurs in hypobaric hypoxia. This study also indicates the appropriate period for drug administration during exposure to hypobaric hypoxia and establishes ionotropic receptors of glutamate as potential therapeutic targets for ameliorating high‐altitude‐induced cognitive dysfunction. © 2007 Wiley‐Liss, Inc.