Deficits of neuronal glutamatergic markers in the caudate nucleus in schizophrenia.
Abnormal glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia. In the present study we investigated two potential neuronal glutamatergic markers, the Excitatory Amino Acid Transporter 3 (EAAT3) and the Vesicular Glutamate Transporter 1 (VGluT1), in post-mortem striatal tissue from control subjects and from subjects with schizophrenia (n = 15 per group). We also investigated the possible influence of chronic antipsychotic administration (typical and atypical) on striatal VGluT1 expression in the rat brain. We found deficits in EAAT3 in all striatal regions examined in schizophrenia when compared to controls. Following correction for confounding factors (post-mortem interval), these deficits only remained significant in the caudate nucleus (p = 0.019). We also found significant deficits in VGluT1 in the caudate nucleus (p = 0.009) in schizophrenia. There were no significant differences in VGluT1 in the striatum of antipsychotic treated rats when compared to their vehicle treated controls. The data provides additional evidence for a glutamatergic synaptic pathology in the caudate nucleus in schizophrenia and may reflect a loss of glutamatergic cortico-striatal pathways. The absence of an effect of antipsychotic administration on VGluT1 indicates that the deficits in schizophrenia are unlikely to be a consequence of pharmacotherapy and thus likely to be a correlate of the disease process.
Nudmamud-Thanoi
S
S
Division of Psychiatry and Neuroscience, Queen's University, Belfast, UK.
Piyabhan
P
P
Harte
M K
MK
Cahir
M
M
Reynolds
G P
GP
D000328:Adult; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D050580:Excitatory Amino Acid Transporter 3 / Q000032:analysis*; D005260:Female; D005973:Glutamine / Q000032:analysis*; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology*; D009435:Synaptic Transmission / Q000187:drug effects; D050598:Vesicular Glutamate Transport Protein 1 / Q000032:analysis*
D050580:Excitatory Amino Acid Transporter 3; C493464:SLC17A7 protein, human; C493400:SLC1A1 protein, human; D050598:Vesicular Glutamate Transport Protein 1; D005973:Glutamine