Transient focal cerebral ischemia significantly alters not only EAATs but also VGLUTs expression in rats: relevance of changes in reactive astroglia.
The involvement of plasma membrane glutamate transporters (EAATs - excitatory aminoacid transporters) in the pathophysiology of ischemia has been widely studied, but little is known about the role of vesicular glutamate transporters (VGLUTs) in the ischemic process. We analyzed the expression of VGLUT1-3 in the cortex and caudate-putamen of rats subjected to transient middle cerebral artery occlusion. Western blot and immunohistochemistry revealed an increase of VGLUT1 signal in cortex and caudate-putamen until 3 days of reperfusion followed by a reduction 7 days after the ischemic insult. By contrast, VGLUT2 and 3 were drastically reduced. Confocal microscopy revealed an increase in VGLUT2 and 3 immunolabelling in the reactive astrocytes of the ischemic corpus callosum and cortex. Changes in VGLUTs and EAATs expression were differently correlated to neurological deficits. Interestingly, changes in VGLUT1 and EAAT2 expression showed a significant positive correlation in caudate-putamen. Taken together, these results suggest a contribution of VGLUTs to glutamate release in these structures, which could promote neuroblast migration and neurogenesis during ischemic recovery, and a possible interplay with EAATs in the regulation of glutamate levels, at least in the first stages of ischemic recovery.
Sánchez-Mendoza
Eduardo
E
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain.
Burguete
María C
MC
Castelló-Ruiz
María
M
González
María Pilar
MP
Roncero
Cesáreo
C
Salom
Juan B
JB
Arce
Carmen
C
Cañadas
Sixta
S
Torregrosa
Germán
G
Alborch
Enrique
E
Oset-Gasque
María Jesús
MJ
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism*
D050491:Glutamate Plasma Membrane Transport Proteins; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid