Abstract
Antidepressant therapies include drugs with a remarkable structural diversity and non-pharmacological interventions, such as electroconvulsive shock. Although the primary neurochemical effects of these treatments may differ, the ≥2- to 3-wk lag in therapeutic onset has led to the hypothesis that adaptive changes in a final common pathway are required for an antidepressant action. Based on this hypothesis, we sought to identify and characterize common changes in gene expression following chronic antidepressant treatments. We utilized a differential display strategy to identify genes that were differentially expressed in mice following chronic treatment with imipramine and electroconvulsive shock. Differential display PCR followed by subcloning, screening by reverse Northern blot, and confirmation by Northern blot revealed a significant increase in the expression of one gene candidate from mouse cortex following antidepressant treatments. The sequence of this 193-bp gene candidate was an exact match to the DNA sequence of mouse mitochondrial cytochrome b. In contrast to the increased mRNA levels of cytochrome b found in cortex, chronic treatment with these antidepressants did not alter mRNA levels in hippocampus, cerebellum, or liver. Moreover, no differences in cortical levels of cytochrome b mRNA were observed after either acute antidepressant treatments or chronic treatment with nonantidepressant drugs (haloperidol and morphine). The observation that chronic, but not acute treatment with imipramine and electroconvulsive shock produces a region-specific change in the levels of mRNA encoding cytochrome b suggests that this enzyme may be involved in the sequence of events resulting in an antidepressant action.
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Andrews J. M. and Nemeroff C. B. (1994) Comtemporary management of depression.Am. J. Med. 97(S 6A), 24S-32S.
Bibb M. J., Van Etten R. A., Wright C. T., Walberg M. W., and Clayton D. A. (1981) Sequence and gene organization of mouse mitochondrial DNA.Cell 26, 167–180.
Chandrasekaran K., Giordano T, Brady D. R., Stoll J., Martin L. J., and Rapoport S. I. (1994) Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease.Mol. Brain Res. 24, 336–340.
Chomezynski P. and Sacchi N. (1987) Single step method of RNA isolation by acid quanidinium thiocyanate-phenol-chloroform extraction.Anal. Biochem. 162, 156–159.
Church G. M. and Gilbert W. (1984) Genomic sequencing.Proc. Natl. Acad. Sci. USA 81, 1991–1995.
Crowe R. R. (1984) Electroconvulsive therapy—a current perspective.N. Engl. J. Med. 311, 163–167.
Douglass J., McKinzie A. A., and Couceyro P. (1995) PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine.J. Neurosci. 15, 2471–2481.
Drevets W. C., Videen T. O., Price J. L., Preskorn S. H., Carmichael S. T., and Raichle M. E. (1992) A functional anatomical study of unipolar depression.J. Neurosci. 12, 3628–3641.
Drevets W. C., Price J. L., Simpson J. R. Jr., Todd R. D., Reich T., Vannier M., et al. (1997) Subgenual prefrontal cortex abnormalities in mood disorders.Nature 386, 824–827.
Duman R. S., Nibuya M., and Vaidya V. A. (1997) A role for CREB in antidepressant action, inAntidepressants: New Pharmacological Strategies (Skolnick P., ed.), Humana, Totowa, NJ, pp. 173–194.
Hatanpaa K., Brady D. R., Stoll J., Rapoport S. I., and Chandrasekaran K. (1996) Neuronal activity and early neurofibrillary tangles in Alzheimer's disease.Ann. Neurol. 40, 411–420.
Heninger G. R., Delgado P. L., and Charney D. S. (1996) The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans.Pharmacopsychiatry 29, 2–11.
Hollister L. E. (1986) Current antidepressants.Ann. Rev. Pharmacol. Toxicol. 26, 23–37.
Huang N.-Y., Layer R. T., and Skolnick P. (1997) Is an adaptation ofN-methyl-d-aspartate (NMDA) receptors an obligatory step in antidepressant action? inAntidepressants: New Pharmacological Strategies (Skolnick P., ed.), Humana, Totowa, NJ, pp. 125–143.
Liang P. and Pardee A. B. (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction.Science 257, 967–971.
Liang P., Zhu W., Zhang X., Guo Z., O'Connell R. P., Averboukh L., et al. (1994) Differential display using one-base anchored oligo-dT primers.Nucleic Acids Res. 22, 5763–5764.
Livesey F. J. and Hunt S. P. (1996) Identifying changes in gene expression in the nervous system: mRNA differential display.TINS 19, 84–88.
Nibuya M., Morinobu S., and Duman R. S. (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.J. Neurosci. 15, 7539–7547.
Nibuya M., Nestler E. J., and Duman R. S. (1996) Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.J. Neurosci. 16, 2365–2372.
Nowak G., Li Y., and Paul I. A. (1996) Adaptation of cortical but not hippocampal NMDA receptors after chronic citalopram treatment.Eur. J. Pharmacol. 295, 75–85.
Passero S., Nardini M., and Battistini N. (1995) Regional cerebral blood flow changes following chronic administration of antidepressant drugs.Prog. Neuro-Psychopharmacol. Biol. Psychiat. 19, 627–636.
Paul I. A., Nowak G., Layer R. T., Popik P., and Skolnick P. (1994) Adaptation of theN-methyl-d-Aspartate receptor complex following chronic antidepressant treatments.J. Pharmacol. Exp. Ther. 269, 95–102.
Richelson E. (1994) Pharmacology of antidepressants—characteristics of the ideal drug.Mayo Clin. Proc. 69, 1069–1081.
Rossby S. P. and Sulser F. (1997) Antidepressants: beyond the synapse, inAntidepressants: New Pharmacological Strategies (Skolnick P., ed.), Humana, Totowa, NJ, pp. 195–212.
Schwaninger M., Schofl C., Blume R., Rossig L., and Knepel W. (1995) Inhibition by antidepressant drugs of cyclic AMP response element-binding protein/cyclic AMP response element-directed gene transcription.Mol. Pharmacol. 47, 1112–1118.
Shader R. I., Fogelman S. M., and Greenblatt D. J. (1997) Newer antidepressants: further reflections.J. Clin. Psychopharmacol. 17, 75–77.
Skolnick P., Layer R. T., Popik P., Nowak G., Paul I. A., and Trullas R. (1996) Adaptation of N-methyl-D-aspartate (NMDA) receptors following antidepressant treatment: implications for the pharmacotherapy of depression.Pharmacopsychiatry 29, 23–26.
Stone E. A. (1983) Problems with the curent catecholamine hypothesis of antidepressant agents: speculations leading to a new hypothesis.Behav. Brain Sci. 6, 555–577.
Stryer L. (1988)Biochemistry, 3rd ed. W. H. Freeman, New York.
Sugrue M. F. (1985) Delayed biochemical changes following antidepressant treatment.Psychopharmacol. Bull. 21, 619–622.
Vetulani J. (1991) The development of our understanding of the mechanism of action of antidepressant drugs.Pol. J. Pharmacol. Pharm. 43, 323–338.
Vetulani J. and Sulser F. (1975) Action of various antidepressant treatments reduces reactivity of noradrenergic cyclic AMP generating system in limbic forebrain.Nature 257, 495–496.
Wang X., Ruffolo R. R. Jr., and Feuerstein G. Z. (1996) mRNA Differential display: application in the discovery of novel pharmacological targets.TIPS 17, 276–279.
Whatley S. A., Curti D., and Marchbanks R. M. (1996) Mitochondrial involvement in schizophrenia and other functional psychoses.Neurochem. Res. 21, 995–1004.
Wong M. L., Khatri P., Licinio J., Esposito A., and Gold P. W. (1996) Identification of hypothalamic transcripts upregulated by antidepressants.Biochem. Biophys. Res. Commun. 229, 275–279.
Wu H. C. and Lee E. H. Y. (1997) Identification of a rat brain gene associated with aging by PCR differential display method.J. Mol. Neurosci. 8, 13–18.
Yakovlev A. G. and Faden A. I. (1995) Molecular strategies in CNS injury.J. Neurotrauma 12, 767–777.
Yee F. and Yolken R. H. (1997) Identification of differentially expressed RNA transcripts in neuropsychiatric disorders.Biol. Psychiatr. 41, 759–761.
Zhang H., Zhang R., and Liang P. (1996) Differential screening of gene expression difference enriched by differential display.Nucleic Acids Res. 24, 2454–2455.
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Dr. Strakhova contributed equally to the study and should be considered a co-lead author.
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Huang, NY., Strakhova, M., Layer, R.T. et al. Chronic antidepressant treatments increase cytochrome b mRNA levels in mouse cerebral cortex. J Mol Neurosci 9, 167–176 (1997). https://doi.org/10.1007/BF02800499
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DOI: https://doi.org/10.1007/BF02800499