Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia.
A disturbance of glutamatergic transmission has been suggested to contribute to the development of schizophrenic pathophysiology based primarily on the ability of glutamate receptor antagonists to induce schizophrenic-like symptoms, and recent studies suggesting reduced glutamatergic function in the prefrontal cortex (PFC) of individuals with a diagnosis of schizophrenia. In order to investigate this hypothesis further, the expression of several 'glutamatergic' markers, the metabotropic glutamate receptors (mGluRs; mGluR3, 5) and the human excitatory amino acid transporter (EAAT2) were compared in the PFC of normal individuals and schizophrenics. The present results showed that glial cells in the pyramidal layers of the PFC from schizophrenics had decreased EAAT2 mRNA content relative to controls in Brodmann areas 9 and 10. The cellular levels of expression of the two mGluR signals investigated (mGluR3, and 5) were not significantly changed relative to controls except for an increase in the neuronal mGluR5 in the pyramidal cell layers of area 11. Comparing the ratio of cellular mGluR expression to that of EAAT2, the mGluR/EAAT2 ratio showed that schizophrenics had a significantly increased mGluR/EAAT2 ratios in the pyramidal cell layers of all three PFC regions examined. The glutamate content of consecutive sections analyzed by high pressure liquid chromatography (HPLC), although decreased in schizophrenics did not reach significance and did not correlate with either EAAT2 or mGluR mRNA content. These results are discussed in the light of current results on the neurochemistry and pharmacology of schizophrenia.
Ohnuma
T
T
Department of Psychiatry, Juntendo University School of Medicine 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Augood
S J
SJ
Arai
H
H
McKenna
P J
PJ
Emson
P C
PC
D000368:Aged; D000369:Aged, 80 and over; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis* / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
D027342:Excitatory Amino Acid Transporter 2; C578935:GRM5 protein, human; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D017981:Receptors, Neurotransmitter; C102718:metabotropic glutamate receptor 3