Antipsychotic-induced gene regulation in multiple brain regions

Matthew James Girgenti, Laura K. Nisenbaum, Franklin Bymaster, Rosemarie Terwilliger, Ronald S. Duman, Samuel Sathyanesan Newton

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The molecular mechanism of action of antipsychotic drugs is not well understood. Their complex receptor affinity profiles indicate that their action could extend beyond dopamine receptor blockade. Single gene expression studies and high-throughput gene profiling have shown the induction of genes from several molecular classes and functional categories. Using a focused microarray approach, we investigated gene regulation in rat striatum, frontal cortex, and hippocampus after chronic administration of haloperidol or olanzapine. Regulated genes were validated by in situ hybridization, real-time PCR, and immunohistochemistry. Only limited overlap was observed in genes regulated by haloperidol and olanzapine. Both drugs elicited maximal gene regulation in the striatum and least in the hippocampus. Striatal gene induction by haloperidol was predominantly in neurotransmitter signaling, G-protein coupled receptors, and transcription factors. Olanzapine prominently induced retinoic acid and trophic factor signaling genes in the frontal cortex. The data also revealed the induction of several genes that could be targeted in future drug development efforts. The study uncovered the induction of several novel genes, including somatostatin receptors and metabotropic glutamate receptors. The results demonstrating the regulation of multiple receptors and transcription factors suggests that both typical and atypical antipsychotics could possess a complex molecular mechanism of action.

Original languageEnglish (US)
Pages (from-to)175-187
Number of pages13
JournalJournal of Neurochemistry
Volume113
Issue number1
DOIs
StatePublished - Apr 1 2010

Fingerprint

Gene expression
Antipsychotic Agents
Brain
olanzapine
Genes
Haloperidol
Frontal Lobe
Transcription Factors
Hippocampus
Somatostatin Receptors
Metabotropic Glutamate Receptors
Dopamine Receptors
Corpus Striatum
Microarrays
G-Protein-Coupled Receptors
Tretinoin
Pharmaceutical Preparations
Neurotransmitter Agents
Rats
Throughput

Keywords

  • Drug target
  • Gene expression
  • Haloperidol
  • Microarray
  • Olanzapine
  • Striatum

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Girgenti, M. J., Nisenbaum, L. K., Bymaster, F., Terwilliger, R., Duman, R. S., & Newton, S. S. (2010). Antipsychotic-induced gene regulation in multiple brain regions. Journal of Neurochemistry, 113(1), 175-187. https://doi.org/10.1111/j.1471-4159.2010.06585.x

Antipsychotic-induced gene regulation in multiple brain regions. / Girgenti, Matthew James; Nisenbaum, Laura K.; Bymaster, Franklin; Terwilliger, Rosemarie; Duman, Ronald S.; Newton, Samuel Sathyanesan.

In: Journal of Neurochemistry, Vol. 113, No. 1, 01.04.2010, p. 175-187.

Research output: Contribution to journalArticle

Girgenti, MJ, Nisenbaum, LK, Bymaster, F, Terwilliger, R, Duman, RS & Newton, SS 2010, 'Antipsychotic-induced gene regulation in multiple brain regions', Journal of Neurochemistry, vol. 113, no. 1, pp. 175-187. https://doi.org/10.1111/j.1471-4159.2010.06585.x
Girgenti, Matthew James ; Nisenbaum, Laura K. ; Bymaster, Franklin ; Terwilliger, Rosemarie ; Duman, Ronald S. ; Newton, Samuel Sathyanesan. / Antipsychotic-induced gene regulation in multiple brain regions. In: Journal of Neurochemistry. 2010 ; Vol. 113, No. 1. pp. 175-187.
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