TY - JOUR
T1 - Localization of the Na+-coupled neutral amino acid transporter 2 in the cerebral cortex
AU - Melone, M.
AU - Varoqui, H.
AU - Erickson, J. D.
AU - Conti, F.
PY - 2006
Y1 - 2006
N2 - We studied the distribution and cellular localization of Na+-coupled neutral amino acid transporter 2, a member of the system A family of amino acid transporters, in the rat and human cerebral cortex using immunocytochemical methods. Na+-coupled neutral amino acid transporter 2-positive neurons were pyramidal and non-pyramidal, and Na+-coupled neutral amino acid transporter 2/GABA double-labeling studies revealed that Na+-coupled neutral amino acid transporter 2 was highly expressed by GABAergic neurons. Double-labeling studies with the synaptophysin indicated that rare axon terminals express Na+-coupled neutral amino acid transporter 2. Na+-coupled neutral amino acid transporter 2-immunoreactivity was also found in astrocytes, leptomeninges, ependymal cells and choroid plexus. Electron microscopy showed robust Na+-coupled neutral amino acid transporter 2-immunoreactivity in the somato-dendritic compartment of neurons and in glial processes, but, as in the case of double-labeling studies, failed to reveal Na+-coupled neutral amino acid transporter 2-immunoreactivity in terminals. To rule out the possibility that the absence of Na+-coupled neutral amino acid transporter 1-[Melone M, Quagliano F, Barbaresi P, Varoqui H, Erickson JD, Conti F (2004) Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring structures, with a note on its localization in human cortex. Cereb Cortex 14:562-574] and Na+-coupled neutral amino acid transporter 2-positive terminals was due to insufficient antigen detection, we evaluated Na+-coupled neutral amino acid transporter 1/synaptophysin and Na+-coupled neutral amino acid transporter 2/synaptophysin coexpression using non-standard immunocytochemical procedures and found that Na+-coupled neutral amino acid transporter 1 and Na+-coupled neutral amino acid transporter 2+ terminals were rare in all conditions. These findings indicate that Na+-coupled neutral amino acid transporter 1 and Na+-coupled neutral amino acid transporter 2 are virtually absent in cortical terminals, and suggest that they do not contribute significantly to replenishing the Glu and GABA transmitter pools through the glutamate-glutamine cycle. The strong expression of Na+-coupled neutral amino acid transporter 2 in the somato-dendritic compartment and in non-neuronal elements that are integral parts of the blood-brain and brain-cerebrospinal fluid barrier suggests that Na+-coupled neutral amino acid transporter 2 plays a role in regulating the levels of Gln and other amino acids in the metabolic compartment of cortical neurons.
AB - We studied the distribution and cellular localization of Na+-coupled neutral amino acid transporter 2, a member of the system A family of amino acid transporters, in the rat and human cerebral cortex using immunocytochemical methods. Na+-coupled neutral amino acid transporter 2-positive neurons were pyramidal and non-pyramidal, and Na+-coupled neutral amino acid transporter 2/GABA double-labeling studies revealed that Na+-coupled neutral amino acid transporter 2 was highly expressed by GABAergic neurons. Double-labeling studies with the synaptophysin indicated that rare axon terminals express Na+-coupled neutral amino acid transporter 2. Na+-coupled neutral amino acid transporter 2-immunoreactivity was also found in astrocytes, leptomeninges, ependymal cells and choroid plexus. Electron microscopy showed robust Na+-coupled neutral amino acid transporter 2-immunoreactivity in the somato-dendritic compartment of neurons and in glial processes, but, as in the case of double-labeling studies, failed to reveal Na+-coupled neutral amino acid transporter 2-immunoreactivity in terminals. To rule out the possibility that the absence of Na+-coupled neutral amino acid transporter 1-[Melone M, Quagliano F, Barbaresi P, Varoqui H, Erickson JD, Conti F (2004) Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring structures, with a note on its localization in human cortex. Cereb Cortex 14:562-574] and Na+-coupled neutral amino acid transporter 2-positive terminals was due to insufficient antigen detection, we evaluated Na+-coupled neutral amino acid transporter 1/synaptophysin and Na+-coupled neutral amino acid transporter 2/synaptophysin coexpression using non-standard immunocytochemical procedures and found that Na+-coupled neutral amino acid transporter 1 and Na+-coupled neutral amino acid transporter 2+ terminals were rare in all conditions. These findings indicate that Na+-coupled neutral amino acid transporter 1 and Na+-coupled neutral amino acid transporter 2 are virtually absent in cortical terminals, and suggest that they do not contribute significantly to replenishing the Glu and GABA transmitter pools through the glutamate-glutamine cycle. The strong expression of Na+-coupled neutral amino acid transporter 2 in the somato-dendritic compartment and in non-neuronal elements that are integral parts of the blood-brain and brain-cerebrospinal fluid barrier suggests that Na+-coupled neutral amino acid transporter 2 plays a role in regulating the levels of Gln and other amino acids in the metabolic compartment of cortical neurons.
KW - glutamate
KW - glutamine-glutamate cycle
KW - human
KW - neutral amino acids
KW - rat
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UR - http://www.scopus.com/inward/citedby.url?scp=33646522176&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2006.02.042
DO - 10.1016/j.neuroscience.2006.02.042
M3 - Article
C2 - 16616430
AN - SCOPUS:33646522176
VL - 140
SP - 281
EP - 292
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 1
ER -