Indispensability of the glutamate transporters GLAST and GLT1 to brain development

Toshiko R. Matsugami, Kentaro Tanemura, Michihiro Mieda, Reiko Nakatomi, Keiko Yamada, Takashi Kondo, Masaharu Ogawa, Kunihiko Obata, Masahiko Watanabe, Tsutomu Hashikawa, Kohichi Tanaka

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)12161-12166
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number32
DOIs
Publication statusPublished - 2006 Aug 8

Keywords

  • Axon/dendrite development
  • Cortex
  • Radial fiber

ASJC Scopus subject areas

  • General

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