Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice

To study the function of GLAST, a glutamate transporter highly expressed in the cerebellar Bergmann astrocytes, the mouse GLAST gene was inactivated. GLAST‐deficient mice developed normally and could manage simple coordinated tasks, such as staying on a stationary or a slowly rotating rod, but failed more challenging task such as staying on a quickly rotating rod. Electrophysiological examination revealed that Purkinje cells in the mutant mice remained to be multiply innervated by climbing fibres even at the adult stage. We also found that oedema volumes in the mutant mice increased significantly after cerebellar injury. These results indicate that GLAST plays active roles both in the cerebellar climbing fibre synapse formation and in preventing excitotoxic cerebellar damage after acute brain injury.

[1]  Masahiko Watanabe,et al.  Glutamate Transporter GLAST Is Expressed in the Radial Glia–Astrocyte Lineage of Developing Mouse Spinal Cord , 1997, The Journal of Neuroscience.

[2]  Y. Inoue,et al.  Structure and functional expression of the cloned mouse neuronal high-affinity glutamate transporter. , 1997, Brain Research. Molecular Brain Research.

[3]  Masahiko Watanabe,et al.  Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. , 1997, Science.

[4]  Susumu Tonegawa,et al.  Persistent Multiple Climbing Fiber Innervationof Cerebellar Purkinje Cellsin Mice Lacking mGluR1 , 1997, Neuron.

[5]  D. Attwell,et al.  Postsynaptic glutamate uptake in rat cerebellar Purkinje cells. , 1996, The Journal of physiology.

[6]  Dimitri M Kullmann,et al.  LTP of AMPA and NMDA Receptor–Mediated Signals: Evidence for Presynaptic Expression and Extrasynaptic Glutamate Spill-Over , 1996, Neuron.

[7]  Masahiko Watanabe,et al.  EAAT4 is a post-synaptic glutamate transporter at Purkinje cell synapses. , 1996, Neuroreport.

[8]  J. Clements.  Transmitter timecourse in the synaptic cleft: its role in central synaptic function , 1996, Trends in Neurosciences.

[9]  K. Tanaka,et al.  Genomic organization, promoter analysis, and chromosomal localization of the gene for the mouse glial high-affinity glutamate transporter Slc1a3. , 1996, Genomics.

[10]  L. Trussell,et al.  Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  M. Hediger,et al.  Knockout of Glutamate Transporters Reveals a Major Role for Astroglial Transport in Excitotoxicity and Clearance of Glutamate , 1996, Neuron.

[12]  Y. Inoue,et al.  Dynamic changes in expression of glutamate transporter mRNAs in developing brain , 1996, Neuroreport.

[13]  H. Kawakami,et al.  Expression of three glutamate transporter subtype mRNAs in human brain regions and peripheral tissues. , 1996, Brain research. Molecular brain research.

[14]  Richard F. Thompson,et al.  Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKCγ mutant mice , 1995, Cell.

[15]  S. Tonegawa,et al.  Impaired synapse elimination during cerebellar development in PKCγ mutant mice , 1995, Cell.

[16]  J. Storm-Mathisen,et al.  Glutamate transporters in glial plasma membranes: Highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry , 1995, Neuron.

[17]  D. Attwell,et al.  Pre- and postsynaptic determinants of EPSC waveform at cerebellar climbing fiber and parallel fiber to Purkinje cell synapses , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  A. Levey,et al.  Selective loss of glial glutamate transporter GLT‐1 in amyotrophic lateral sclerosis , 1995, Annals of neurology.

[19]  M. Kavanaugh,et al.  An excitatory amino-acid transporter with properties of a ligand-gated chloride channel , 1995, Nature.

[20]  K. Tanaka,et al.  Molecular cloning of two glutamate transporter subtypes from mouse brain. , 1995, Biochimica et biophysica acta.

[21]  Youngnam Kang,et al.  Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluRδ2 mutant mice , 1995, Cell.

[22]  H. Dodt,et al.  Novel forms of neuronal migration in the rat cerebellum , 1995, Journal of neuroscience research.

[23]  D. Attwell,et al.  Triggering and execution of neuronal death in brain ischaemia: two phases of glutamate release by different mechanisms , 1994, Trends in Neurosciences.

[24]  Gang Tong,et al.  Block of glutamate transporters potentiates postsynaptic excitation , 1994, Neuron.

[25]  S. Tonegawa,et al.  Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice , 1994, Cell.

[26]  S. Tonegawa,et al.  Reduced hippocampal long-term potentiation and context-specific deficit in associative learning in mGluR1 mutant mice , 1994, Cell.

[27]  A. Levey,et al.  Localization of neuronal and glial glutamate transporters , 1994, Neuron.

[28]  Boris Barbour,et al.  Prolonged presence of glutamate during excitatory synaptic transmission to cerebellar Purkinje cells , 1994, Neuron.

[29]  E. Seeberg,et al.  Differential Expression of Two Glial Glutamate Transporters in the Rat Brain: an In Situ Hybridization Study , 1994, The European journal of neuroscience.

[30]  T. Yagi,et al.  A novel negative selection for homologous recombinants using diphtheria toxin A fragment gene. , 1993, Analytical biochemistry.

[31]  Kohichi Tanaka.  Cloning and expression of a glutamate transporter from mouse brain , 1993, Neuroscience Letters.

[32]  C. Piantadosi,et al.  Cold-induced brain edema in mice. Involvement of extracellular superoxide dismutase and nitric oxide. , 1993, The Journal of biological chemistry.

[33]  P. Rakic,et al.  Modulation of neuronal migration by NMDA receptors. , 1993, Science.

[34]  Kohichi Tanaka.  Expression cloning of a rat glutamate transporter , 1993, Neuroscience Research.

[35]  M. Hediger,et al.  Primary structure and functional characterization of a high-affinity glutamate transporter , 1992, Nature.

[36]  E. Seeberg,et al.  Cloning and expression of a rat brain L-glutamate transporter , 1992, Nature.

[37]  T. Storck,et al.  Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[38]  A. Konnerth,et al.  Potentiation of GABA-mediated currents by cAMP-dependent protein kinase. , 1992, Neuroreport.

[39]  J. Rothstein,et al.  Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. , 1992, The New England journal of medicine.

[40]  A. Konnerth,et al.  Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells , 1992, Nature.

[41]  M. Hunter-Ensor,et al.  Pharmacologically distinct sodium-dependentl-[3H]glutamate transport processes in rat brain , 1991, Brain Research.

[42]  A. Konnerth,et al.  Synaptic‐ and agonist‐induced excitatory currents of Purkinje cells in rat cerebellar slices. , 1991, The Journal of physiology.

[43]  R. Vink,et al.  Effect of Noncompetitive Blockade of N‐Methyl‐d‐Aspartate Receptors on the Neurochemical Sequelae of Experimental Brain Injury , 1990, Journal of neurochemistry.

[44]  S. Christakos,et al.  Calcium binding protein (calbindin-D28k) gene expression in the developing and aging mouse cerebellum. , 1990, Brain research. Molecular brain research.

[45]  Andrew P. McMahon,et al.  The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain , 1990, Cell.

[46]  A. Konnerth,et al.  Synaptic currents in cerebellar Purkinje cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[47]  R. Vink,et al.  The role of excitatory amino acids and NMDA receptors in traumatic brain injury. , 1989, Science.

[48]  C. Cotman,et al.  The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. , 1989, Annual review of pharmacology and toxicology.

[49]  D. Choi,et al.  Glutamate neurotoxicity and diseases of the nervous system , 1988, Neuron.

[50]  S. Schuldiner,et al.  Mechanism of Transport and Storage of Neurotransmitter , 1987 .

[51]  S. Schuldiner,et al.  Mechanism of transport and storage of neurotransmitters. , 1987, CRC critical reviews in biochemistry.

[52]  Masao Ito.  The Cerebellum And Neural Control , 1984 .

[53]  T. Iwanaga,et al.  Isolation and immunohistochemical localization of a cerebellar protein , 1984, Neuroscience Letters.

[54]  F. Crépel.  Regression of functional synapses in the immature mammalian cerebellum , 1982, Trends in Neurosciences.

[55]  V. Sapirstein,et al.  Development of membrane-bound carbonic anhydrase and glial fibrillary acidic protein in normal and quaking mice. , 1982, Brain research.

[56]  E. Weibel.  Practical methods for biological morphometry , 1979 .

[57]  S. Palay,et al.  Functional Architectonics without Numbers , 1974 .

[58]  Prof. Dr. Sanford L. Palay,et al.  Cerebellar Cortex , 1974, Springer Berlin Heidelberg.

[59]  E. Weibel,et al.  Principles and methods for the morphometric study of the lung and other organs. , 1963, Laboratory investigation; a journal of technical methods and pathology.