Effects of schizophrenomimetics on the expression of the CCN1 (CYR 61) gene encoding a matricellular protein in the infant and adult neocortex of the mouse and rat.
The acute systemic administration of a schizophrenomimetic phencyclidine [5 or 10 mg/kg, subcutaneously (s.c.)] markedly up-regulated the neocortical expression of the CCN1 gene encoding a secreted extracellular matrix-associated protein at postnatal day 56, but not at postnatal day 8, after 60 min in the mouse and rat. The development-dependent nature of the up-regulation between postnatal days 8 and 56 seems to be similar to that of the adult type phencyclidine-induced abnormal behaviours, which have been considered to be models of schizophrenic symptoms. In the young adult rat, 5, 10, and 20 mg/kg phencyclidine (given s.c.) induced an increase in the CCN1 gene transcripts in a dose-related and bell-shaped manner with a maximum at the dose of 10 mg/kg, 60 min post-injection. Other schizophrenomimetics, dizocilpine (1 mg/kg) and methamphetamine (4.8 mg/kg), also caused a prominent up-regulation of the neocortical expression of the CCN1 gene in adult rats. These results indicate that the CCN1 gene or protein could be implicated in a molecular cascade associated with the age-dependent onset of schizophrenia that usually occurs after puberty.
Ito
Takashi
T
Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Hiraoka
Shuichi
S
Kuroda
Yasukazu
Y
Ishii
Sumikazu
S
Umino
Asami
A
Kashiwa
Atsushi
A
Yamamoto
Naoki
N
Kurumaji
Akeo
A
Nishikawa
Toru
T
D000818:Animals; D015152:Blotting, Northern; D055515:Cysteine-Rich Protein 61; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010622:Phencyclidine; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000139:chemically induced* / Q000235:genetics*; D012565:Schizophrenic Psychology; D015854:Up-Regulation / Q000187:drug effects
C491850:CCN1 protein, mouse; C501849:CCN1 protein, rat; D055515:Cysteine-Rich Protein 61; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D012313:RNA; D004247:DNA; D010622:Phencyclidine