title: Characteristic development of the GABA-removal system in the mouse spinal cord.
abstract: GABA is a predominant inhibitory neurotransmitter in the CNS. Released GABA is removed from the synaptic cleft by two GABA transporters (GATs), GAT-1 and GAT-3, and their dysfunction affects brain functions. The present study aimed to reveal the ontogeny of the GABA-removal system by examining the immunohistochemical localization of GAT-1 and GAT-3 in the embryonic and postnatal mouse cervical spinal cord. In the dorsal horn, GAT-1 was localized within the presynapses of inhibitory axons after embryonic day 15 (E15), a little prior to GABAergic synapse formation. The GAT-1-positive dots increased in density until postnatal day 21 (P21). By contrast, in the ventral horn, GAT-1-positive dots were sparse during development, although many transient GABAergic synapses were formed before birth. GAT-3 was first localized within the radial processes of radial glia in the ventral part on E12 and the dorsal part on E15. The initial localization of the GAT-3 was almost concomitant with the dispersal of GABAergic neurons. GAT-3 continued to be localized within the processes of astrocytes, and increased in expression until P21. These results suggested the following: (1) before synapse formation, GABA may be transported into the processes of radial glia or immature astrocytes by GAT-3. (2) At the transient GABAergic synapses in the ventral horn, GABA may not be reuptaken into the presynapses. (3) In the dorsal horn, GABA may start to be reuptaken by GAT-1 a little prior to synapse formation. (4) After synapse formation, GAT-3 may continue to remove GABA from immature and mature synaptic clefts into the processes of astrocytes. (5) Development of the GABA-removal system may be completed by P21.
authors.affiliation: Department of Molecular Anatomy, School of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 9030215, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Molecular Anatomy, School of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 9030215, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Department of Molecular Anatomy, School of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 9030215, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Shimizu-Okabe
authors.affiliation: Department of Molecular Anatomy, School of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 9030215, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Niizaki
authors.affiliation: Department of Molecular Anatomy, School of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 9030215, Japan. Electronic address: takachan@med.u-ryukyu.ac.jp.
authors.forename: C
authors.initials: C
authors.lastname: Takayama
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D002574:Cervical Vertebrae; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D064231:Nestin / Q000378:metabolism; D020671:Posterior Horn Cells / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; C577485:Nes protein, mouse; D064231:Nestin; C493414:Slc6a1 protein, mouse; C493419:Slc6a13 protein, mouse; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D005680:gamma-Aminobutyric Acid
keywords: GABA transporter 1 (GAT-1); GABA transporter 3 (GAT-3); GABAergic synapse; astrocyte; radial glia; vesicular GABA transporter (VGAT)