From the Cover: Indispensability of the glutamate transporters GLAST and GLT1 to brain development.
Previous in vitro studies have shown that the neurotransmitter glutamate is important in brain development. Paradoxically, loss-of-function mouse models of glutamatergic signaling that are generated by genetic deletion of glutamate receptors or glutamate release show normal brain assembly. We examined the direct consequences on brain development of extracellular glutamate buildup due to the depletion of the glutamate transporters GLAST and GLT1. GLAST/GLT1 double knockout mice show multiple brain defects, including cortical, hippocampal, and olfactory bulb disorganization with perinatal mortality. Here, we report abnormal formation of the neocortex in GLAST/GLT1 mutants. Several essential aspects of neuronal development, such as stem cell proliferation, radial migration, neuronal differentiation, and survival of SP neurons, were impaired. These results provide direct in vivo evidence that GLAST and GLT1 are necessary for brain development through regulation of extracellular glutamate concentration and show that an important mechanism is likely to be maintenance of glutamate-mediated synaptic transmission.
Matsugami
Toshiko R
TR
Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
Tanemura
Kentaro
K
Mieda
Michihiro
M
Nakatomi
Reiko
R
Yamada
Keiko
K
Kondo
Takashi
T
Ogawa
Masaharu
M
Obata
Kunihiko
K
Watanabe
Masahiko
M
Hashikawa
Tsutomu
T
Tanaka
Kohichi
K
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000473:pathology / Q000502:physiology*; D002540:Cerebral Cortex / Q000473:pathology; D003712:Dendrites / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1 / Q000502:physiology*; D027342:Excitatory Amino Acid Transporter 2 / Q000502:physiology*; D017353:Gene Deletion; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000378:metabolism
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid