Loss of glial glutamate transporters and induction of neuronal expression of GLT-1B in the hypoxic neonatal pig brain.
The homeostasis of glutamate is critical to normal brain function; deficiencies in the regulation of extracellular glutamate are thought to be a major determinant of damage in hypoxic brains. Extracellular levels of glutamate are regulated mainly by plasmalemmal glutamate transporters. We have evaluated the distribution of the glutamate transporter GLAST and two splice variants of GLT-1 in the hypoxic neonatal pig brain using this as model of neonatal humans. In response to severe hypoxic insults, we observe a rapid loss of two glial glutamate transporters from specific brain regions, such as the CA1 region of the hippocampus, but not the dentate gyrus. The spatial distribution of loss accords with patterns of damage in these brains. Conversely, we demonstrate that hypoxia evokes the expression of a splice variant of GLT-1 in neurons. We suggest that this expression may be induced in response to elevated extracellular glutamate around these neurons, and that this splice variant may represent a useful marker for direct quantification of the extent of likely neuronal damage in hypoxic brains.
Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane 4072, Australia. d.pow@eaats.org
David V
DV
Pow
Taryn
T
Naidoo
Barbara E
BE
Lingwood
Genevieve N
GN
Healy
Susan M
SM
Williams
Robert K P
RK
Sullivan
Stephanie
S
O'Driscoll
Paul B
PB
Colditz
D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis*; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D013552:Swine; D013997:Time Factors
D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid