Expression of glutamate transporter subtypes during normal human corticogenesis and type II lissencephaly.
Glutamate transporters are thought to have an important role in central nervous system (CNS) development. We investigated the expression of the sodium-dependent high-affinity glutamate transporters EAAT1, EAAT2, and EAAT3 in 11 human autopsied cases without neurological disorders and in four cases with type II lissencephaly including Walker Warburg's syndrome (WWS) and Fukuyama-type congenital muscular dystrophy (FCMD), both of which are classified as migration disorders of the human brain. Expression of glutamate transporter subtypes was differentially regulated during normal human corticogenesis. Although EAAT1 and EAAT2 were mainly localized to the cortical astrocytes in the postnatal brain, EAAT1 was enriched in the proliferative zones and radial glia from 13 gestational weeks (GW) to 20 GW. EAAT2 was abundant in the intermediate zone until 23 GW, and transiently expressed in the radial fibers of the transitional form of radial glia into mature astrocytes as well as partly in the corticofugal axonal bundles. EAAT3 immunoreactivity was robust in the apical dendrites of the pyramidal neurons in the marginal zone and cortical plate during corticogenesis, and decreased postnatally. In the individuals with type II lissencephaly, glutamate transporters were expressed in the extrusion of neuroglial tissue. Bundles of EAAT2-immunoreactive radial fibers were prominent in the specimens at 20 GW. Thus, glutamate transporters are differentially regulated during normal and impaired corticogenesis. Altered glutamate transporter expression in type II lissencephaly suggests that glutamate metabolism is involved in the formation of the normal cortex and contributes to the disorganized cortex seen in migration disorders.
Furuta
Akiko
A
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. afuruta@ncnp.go.jp
Takashima
Sachio
S
Yokoo
Hideaki
H
Rothstein
Jeffrey D
JD
Wada
Keiji
K
Iwaki
Toru
T
D000328:Adult; D000368:Aged; D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis* / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism; D001927:Brain Diseases / Q000235:genetics / Q000473:pathology*; D019070:Cell Lineage / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D003712:Dendrites / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D050491:Glutamate Plasma Membrane Transport Proteins; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D011247:Pregnancy; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics
D027322:Amino Acid Transport System X-AG; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; C493400:SLC1A1 protein, human; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; D027981:Symporters