Increased expression of glutaminase and glutamine synthetase mRNA in the thalamus in schizophrenia.
Numerous molecules enable the handling of glutamate that is destined for neurotransmitter release, including transporters, receptors and glutamatergic enzymes. Previous work in our lab has shown altered levels of transcript expression of excitatory amino acid transporters and a vesicular glutamate transporter in the thalamus in schizophrenia. These changes suggest that molecules that facilitate the release and reuptake of glutamate may be abnormal in schizophrenia. In this study we determined the levels of expression of phosphate activated glutaminase (PAG), which converts glutamine to glutamate, and glutamine synthetase (GS), which converts glutamate to glutamine, with the hypothesis that thalamic PAG and GS transcript expression is altered in schizophrenia. We investigated expression of PAG and GS mRNA using in situ hybridization in six different thalamic nuclei (anterior, dorsomedial, centromedial, ventral anterior, ventral and reticular) from 13 persons with schizophrenia and 8 comparison subjects and found that transcripts for PAG and GS were significantly increased in schizophrenia. Increased PAG and GS transcripts suggest enhanced glutamatergic neurotransmission in the thalamus and its efferent targets in schizophrenia.
Bruneau
Emile G
EG
Mental Health Research Institute and Department of Psychiatry, University of Michigan Medical School, 205 Zina Pitcher Place, Ann Arbor, MI 48109, USA. ebruneau@umich.edu
McCullumsmith
Robert E
RE
Haroutunian
Vahram
V
Davis
Kenneth L
KL
Meador-Woodruff
James H
JH
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis*; D005972:Glutaminase / Q000096:biosynthesis*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D012559:Schizophrenia / Q000201:enzymology*; D013788:Thalamus / Q000201:enzymology*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase