Synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP) is expressed differentially in phencyclidine-treated rats and is increased in the nucleus accumbens of patients with schizophrenia.
Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Therefore, PCP-treated animals can provide a model for schizophrenia. Using differential display, we identified a gene regulated by the delayed action of PCP in rat nucleus accumbens (NAcs). Sequence analysis showed that the cDNA clone obtained was identical to rat synapse-associated protein 90/postsynaptic density-95-associated protein 1 (SAPAP1). Quantitative reverse transcriptase (RT)-PCR analysis showed that SAPAP1 mRNA had increased significantly in rat NAc (P<0.0001) and hippocampus (P<0.01) 24 h after a PCP (10 mg/kg) injection as compared to the controls. Immunoquantification using an anti-SAPAP1 antibody indicated that immunoreactivity for SAPAP1 increased significantly (P&<0.05) in the NAcs of unmedicated patients with schizophrenia, as compared to the control subjects and medicated patients with schizophrenia. Our findings support the hypothesis that there is abnormal glutamatergic neurotransmission in schizophrenia and show evidence of abnormalities in the intracellular signal transduction via N-methyl-D-aspartate (NMDA) receptors.
Kajimoto
Yasuo
Y
Division of Psychiatry and Neurology, Department of Environmental Health and Safety, Kobe University Graduate School of Medicine, Kobe, Japan.
Shirakawa
Osamu
O
Lin
Xian-Hao
XH
Hashimoto
Takeshi
T
Kitamura
Noboru
N
Murakami
Naoya
N
Takumi
Toru
T
Maeda
Kiyoshi
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D015152:Blotting, Northern; D015153:Blotting, Western; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010622:Phencyclidine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074407:SAP90-PSD95 Associated Proteins; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
D014150:Antipsychotic Agents; C000614187:DLGAP1 protein, human; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000074407:SAP90-PSD95 Associated Proteins; D010622:Phencyclidine