Rapid loss of glutamine synthetase from astrocytes in response to hypoxia: implications for excitotoxicity.
We have examined brains of neonatal pigs that were rendered hypoxic. Glutamine synthetase (GS), a key enzyme in the detoxification of glutamate and ammonia, was rapidly lost from astrocytes in regions susceptible to damage, including the CA1 of hippocampus and various cortical regions. Conversely, resilient areas such as the dentate gyrus exhibited little or no loss of GS. Onset of loss was rapid, patches of loss being evident by 1h post-insult, and loss was extensive by 24h and did not recover by 72 h. Examination of counterstained sections revealed that GS losses preceded any overt neuronal damage. Loss of GS from astrocytes would plausibly lead to a rise in intracellular glutamate, and could explain why reversal of astrocytic glutamate transport during hypoxia/ischaemia is conceptually possible.
Lee
Aven
A
The University of Queensland, Centre for Clinical Research, Royal Brisbaneand Womens Hospital, Building 71 Herston, Brisbane, Queensland 4029, Australia.
Lingwood
Barbara E
BE
Bjorkman
S Tracey
ST
Miller
Stephanie M
SM
Poronnik
Philip
P
Barnett
Nigel L
NL
Colditz
Paul
P
Pow
David V
DV
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000201:enzymology*; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D013552:Swine
D005974:Glutamate-Ammonia Ligase