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Catechol-O-methyltransferase gene regulation in rat frontal cortex

Molecular Psychiatry volume 12, pages 322–323 (2007)Cite this article

Catechol-O-methyltransferase (COMT) was first described by Axelrod et al.,1 who later partially purified and characterized this important enzyme.2 COMT is responsible for the O-methylation of catecholamines resulting in modulation and increase in dopamine levels in the prefrontal cortex.3, 4, 5 Recent reports consider COMT as an important gene; which may be involved in cognition, modulation of prefrontal cortex and genetic predisposition towards schizophrenia.5 There is one single gene for COMT, which codes for both soluble and membrane-bound isoforms of COMT.3 Genetic polymorphisms have also been described associating COMT activity with several other neuropsychiatric conditions such as obsessive-compulsive disorder, antisocial behavior, late-onset alcoholism and rapid cycling bipolar disorder.3 Brain COMT is present in neurons,6 glial7 and ependymal cells.6 The soluble COMT is localized to the cytosol and nucleus whereas the membrane-bound COMT is present in the endoplasmic reticulum.3 Male COMT knockout mice lack COMT activity and exhibit a threefold increase in dopamine levels in the frontal cortex.8 Subjects with velocardiofacial syndrome, who have a COMT deletion at chromosome 22q11, exhibit a higher incidence of schizophrenia.5

Recent experiments performed in our laboratory evaluated the effects of chronic administration of several psychotropic agents such as clozapine (20 mg/kg/day), fluoxetine (10 mg/kg/day), haloperidol (1.5 mg/kg/day), lithium chloride (50 mg/kg/day), olanzapine (2 mg/kg/day), sodium valproate (300 mg/kg/day) versus saline, on brain gene regulation, in male Sprague–Dawley albino rats. Animals were randomly assigned to one of the six drug groups or sterile saline and administered drugs or diluent intraperitoneally for 21 days. The University of Minnesota Animal Care Committee approved all experimental procedures. Animals were killed, brains were removed and frontal cortices were dissected and flash-frozen in liquid nitrogen and stored at −80°C for future assays. The tissues were then homogenized and analyzed for DNA and protein levels using DNA microarray technique or sodium dodecyl sulfate-polyacryl amide gel electrophoresis and Western blotting, respectively, following previous procedures.9, 10 Differences for all protein levels for COMT were normalized against β-actin and assayed using a Student's t-test. Significant differences are defined as those with a P-value <0.05.

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References

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  5. Tunbridge EM, Weickert CS, Kleinman JE, Herman MM, Chen J, Kolachana BS et al. Cerebral Cortex 2006 (E-pub ahead of print).

  6. Matsumoto M, Weickert CS, Akil M, Lipska BK, Hyde TM, Herman MM et al. Neuroscience 2003; 116: 127–137.

  7. Karhunen T, Tilgmann C, Ulmanen I, Panula P . Int J Dev Neurosci 1995; 13: 825–834.

  8. Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D et al. Proc Natl Acad Sci USA 1998; 95: 9991–9996.

  9. Fatemi SH, Pearce DA, Brooks AI, Sidwell RW . Synapse 2005; 57: 91–99.

  10. Fatemi SH, Reutiman TJ, Folsom TD, Bell C, Nos L, Fried P et al. Neuropsychopharm 2006; 31: 1888–1899.

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Acknowledgements

We acknowledge the generous support of the Stanley Medical Research Institute.

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  1. Division of Neuroscience Research, Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

    S H Fatemi & T D Folsom

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  1. S H Fatemi
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Correspondence to S H Fatemi.

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Fatemi, S., Folsom, T. Catechol-O-methyltransferase gene regulation in rat frontal cortex. Mol Psychiatry 12, 322–323 (2007). https://doi.org/10.1038/sj.mp.4001958

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