Selective loss of expression of glutamate GluR2/R3 receptor subunits in cerebellar tissue from a patient with olivopontocerebellar atrophy.
Expression of the mRNAs encoding the astrocytic (EAAT1, EAAT2) and neuronal (EAAT3, EAAT4) excitatory amino acid transporters and the AMPA-type glutamate receptor subunits GluR2 and GluR3 was investigated in postmortem cerebellar extracts from a patient with olivopontocerebellar atrophy (OPCA) and in material from three age-matched controls. Decreased expression in the steady state level of EAAT4 mRNA in the OPCA sample was correlated with the selective loss of Purkinje cells. Neuropathological evaluation revealed reactive gliosis and concomitantly increased expression of the mRNA encoding astrocytic glial fibrillary acidic protein (GFAP). Expression of the mRNAs encoding the AMPA receptor subunits GluR2 and GluR3 subunits was found to be decreased in OPCA suggesting that excitotoxic mechanism could play a role in the pathogenesis of the selective neuronal cell death in this disorder.
Dirson
Gregoire
G
Neuroscience Research Unit, Hĵpital Saint-Luc du CHUM University of Montreal, Canada.
Desjardins
Paul
P
Tannenberg
Tony
T
Dodd
Peter
P
Butterworth
Roger F
RF
D000368:Aged; D027322:Amino Acid Transport System X-AG / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D002525:Cerebellar Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D005260:Female; D015870:Gene Expression / Q000502:physiology; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009849:Olivopontocerebellar Atrophies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics*; D017470:Receptors, Glutamate / Q000235:genetics; D027981:Symporters / Q000235:genetics
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C493400:SLC1A1 protein, human; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human; C493391:SLC1A6 protein, human; D027981:Symporters; C104723:glutamate receptor ionotropic, AMPA 3; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2