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Volume 17, Number 21,
Issue of November 1, 1997
pp. 8363-8375
Copyright ©1997 Society for Neuroscience
Glutamate Transporter Protein Subtypes Are Expressed
Differentially during Rat CNS Development
Received May 27, 1997; revised Aug. 15, 1997; accepted Aug. 20, 1997.
Akiko Furuta1,
Jeffrey D. Rothstein1, 2, and
Lee J. Martin2, 3
Departments of 1 Neurology,
2 Neuroscience, and 3 Pathology, Division of
Neuropathology, Johns Hopkins University School of Medicine, Baltimore,
Maryland 21287
Extracellular glutamate concentrations are regulated by glial and
neuronal transporter proteins. Four glutamate transporter subtypes have
been identified in rat brain; GLAST and GLT-1 are primarily astrocytic,
whereas EAAC1 and EAAT4 are neuronal. Using immunoblotting and
immunohistochemistry with subtype-specific antipeptide antibodies, we
examined the protein expression and regional and cellular localization
of each glutamate transporter subtype in embryonic and postnatal rat
CNS. Each transporter had a specific pattern of expression. GLAST
immunoreactivity was low prenatally but became enriched in cerebellar
Bergmann glia early postnatally and then was also present in forebrain
later postnatally. The post-translational modification of GLAST was
unique among the subtypes; glycosylated GLAST increased with
maturation, whereas nonglycosylated protein decreased in abundance
postnatally. GLT-1 was present in fetal brain and spinal cord, with
expression progressively increasing to adult levels throughout the
neuraxis by postnatal day 26. Transient expression of GLT-1
immunoreactivity along axonal pathways was observed prenatally, in
contrast to the exclusive localization of GLT-1 to astrocytes in the
adult CNS. EAAC1, localized to neurons, was enriched in forebrain,
diencephalon, and hindbrain during prenatal and postnatal development.
EAAC1 expression was greater in newborn brain compared with adult
brain. EAAT4 had a region-specific distribution; EAAT4 was mainly in
cerebellum, localized to Purkinje cells, with much lower levels in
forebrain. EAAT4 levels increased in cerebellum with age. We conclude
that during CNS development the expression of glutamate transporter subtypes is differentially regulated, regionally segregated, and coordinated.
Key words:
brain development;
excitatory amino acid;
perinatal brain
damage;
corticogenesis;
excitotoxicity;
striatum
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