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Related Experiment Videos

Phencyclidine-induced changes in rat cortical gene expression identified by microarray analysis: implications for

Sergio Kaiser1, Lisa A Foltz, Carolyn A George

  • 1Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285-0438, USA.

Neurobiology of Disease
|June 23, 2004
PubMed
Summary

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Phencyclidine (PCP) alters gene expression in the rat brain, potentially explaining its schizophrenia-like effects. These changes involve neural pathways and biological processes relevant to psychiatric disorders.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Psychiatry

Background:

  • Phencyclidine (PCP) is an N-methyl-D-aspartate receptor antagonist known to induce schizophrenia-like symptoms.
  • The precise molecular mechanisms underlying PCP's behavioral effects remain poorly understood.

Purpose of the Study:

  • To identify gene expression changes in the rat prefrontal cortex (PFC) induced by acute phencyclidine administration.
  • To explore the relevance of these molecular alterations to schizophrenia.

Main Methods:

  • Oligonucleotide microarray analysis of rat cortical gene expression following acute PCP exposure.
  • Validation of microarray findings using real-time quantitative PCR (RTQ-PCR).
  • Time-course and dose-response studies to confirm and extend gene expression alterations.

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Main Results:

  • Acute phencyclidine significantly altered the expression of 477 genes in the rat PFC.
  • Confirmed gene expression changes ranged from -59% to 255% via RTQ-PCR.
  • Altered genes are involved in stress, inflammation, neural plasticity, signal transduction, and other biological processes.

Conclusions:

  • Phencyclidine-induced gene expression changes in the PFC provide molecular insights into its psychotomimetic effects.
  • Dysregulated genes are linked to thalamocortical projections, neurotransmission, thyroid hormone activity, oligodendrocytes, lipid metabolism, sleep, and velocardiofacial syndrome, suggesting relevance to schizophrenia pathophysiology.