Glutamate transporters in the spinal cord of the wobbler mouse.
We studied the role of glutamate excitotoxicity in motor neuron degeneration in the wobbler mouse (wr/wr), a model of amyotrophic lateral sclerosis and spinal muscular atrophies. Choline acetyltransferase (ChAT) activity was decreased in the cervical spinal cord and in the muscles innervated by nerves originating in this region of wobbler mice, but no differences were found in the lumbar spinal cord and in the hindleg muscles. Glial fibrillar acid protein (GFAP), a marker of reactive gliosis, was significantly higher in the cervical spinal cord of wobbler mice aged 4 weeks than in controls and the differences were more marked at 12 weeks; no differences were found in the lumbar spinal cord. In spite of this selective degeneration of motor neurons (resulting in strong decrease in the neuronal glutamate transporter EAAC1) and reactive gliosis in the cervical spinal cord, the levels of the glial glutamate transporter proteins GLT-1 and GLAST were similar in wobbler and control mice. Plasma concentrations of excitatory amino acids were no different at any time examined. Our results exclude the involvement of decrease in glutamate GLT 1 transporter in the motor neuron degeneration in wobbler mice.
Bigini
P
P
Laboratory of Receptor Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy.
Bastone
A
A
Mennini
T
T
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000002:abnormalities / Q000378:metabolism*; D016472:Motor Neuron Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D027981:Symporters
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D050580:Excitatory Amino Acid Transporter 3; D005904:Glial Fibrillary Acidic Protein; D050491:Glutamate Plasma Membrane Transport Proteins; C493399:Slc1a1 protein, mouse; C493393:Slc1a3 protein, mouse; D027981:Symporters; D018698:Glutamic Acid; D002795:Choline O-Acetyltransferase