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

Int J Neuropsychopharmacol. 2007 Dec;10(6):717-25. doi: 10.1017/S1461145707007882. Epub 2007 Jul 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cysteine-Rich Protein 61
  • DNA / biosynthesis
  • DNA / genetics
  • Down-Regulation / drug effects
  • Excitatory Amino Acid Antagonists
  • Hallucinogens / pharmacology*
  • Immediate-Early Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Neocortex / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Phencyclidine
  • RNA / biosynthesis
  • RNA / genetics
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schizophrenia / chemically induced*
  • Schizophrenia / genetics*
  • Schizophrenic Psychology*
  • Up-Regulation / drug effects

Substances

  • CCN1 protein, mouse
  • CCN1 protein, rat
  • Cysteine-Rich Protein 61
  • Excitatory Amino Acid Antagonists
  • Hallucinogens
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Receptors, N-Methyl-D-Aspartate
  • RNA
  • DNA
  • Phencyclidine