Nuclear orphan receptor Nor-1 contributes to depressive behavior in the Wistar-Kyoto rat model of depression

Daniel J. Schaffer, Elif Tunc-Ozcan, Pradeep Kumar Shukla, Andreja Volenec, Eva E. Redei

Research output: Contribution to journalArticle

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Abstract

The current study explored the effects of prolonged antidepressant treatment on mRNA levels of two nuclear receptors in specific brain regions of an animal model of depression, the Wistar-Kyoto (WKY) rat. Both nuclear receptors have been implicated in the development or treatment of depression. The expression of nuclear orphan receptor-1 (Nor-1), a member of the NR4A nuclear orphan receptor family, is induced by electroconvulsive shock, an effective treatment for depression. Deficit in the levels or function of the glucocorticoid receptor (GR) found in depressed patients has been causally implicated in depression, as this deficit is normalized by antidepressant treatments. Baseline levels of amygdalar Nor-1 and GR mRNA were higher in the WKYs compared to the comparison control Sprague-Dawley rats (SD). Prolonged treatment with the antidepressant desipramine (DMI) decreased the expression of both transcripts in the WKY strain concomitantly with decreased immobility in the forced swim test (FST) of depressive behavior. Using short hairpin RNA (shRNA) targeted against Nor-1, we investigated the direct contribution of elevated Nor-1 expression in the amygdala of WKY to their exaggerated depressive behavior in the FST. After validating the shRNA targeting of Nor-1 in vitro, Nor-1 shRNA containing vector was infused intracerebroventricularly, using a linear polyethylenimine (PEI)-containing in vivo gene delivery system. Repeated administration of Nor-1 shRNA ameliorated the depressive behavior of WKYs in the FST and decreased amygdalar Nor-1 mRNA levels without affecting GR mRNA levels. These data demonstrate that brain region-specific changes in GR expression in response to DMI are strain dependent and that elevated amygdalar Nor-1 expression can contribute to depressive behavior in the WKY model of depression.

Original languageEnglish (US)
Pages (from-to)32-39
Number of pages8
JournalBrain Research
Volume1362
DOIs
StatePublished - Nov 29 2010

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Orphan Nuclear Receptors
Inbred WKY Rats
Depression
Glucocorticoid Receptors
Small Interfering RNA
Antidepressive Agents
Messenger RNA
Desipramine
Cytoplasmic and Nuclear Receptors
Therapeutics
Polyethyleneimine
Gene Transfer Techniques
Electroshock
Brain
Amygdala
Sprague Dawley Rats
Animal Models

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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Nuclear orphan receptor Nor-1 contributes to depressive behavior in the Wistar-Kyoto rat model of depression. / Schaffer, Daniel J.; Tunc-Ozcan, Elif; Shukla, Pradeep Kumar; Volenec, Andreja; Redei, Eva E.

In: Brain Research, Vol. 1362, 29.11.2010, p. 32-39.

Research output: Contribution to journalArticle

Schaffer, Daniel J. ; Tunc-Ozcan, Elif ; Shukla, Pradeep Kumar ; Volenec, Andreja ; Redei, Eva E. / Nuclear orphan receptor Nor-1 contributes to depressive behavior in the Wistar-Kyoto rat model of depression. In: Brain Research. 2010 ; Vol. 1362. pp. 32-39.
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abstract = "The current study explored the effects of prolonged antidepressant treatment on mRNA levels of two nuclear receptors in specific brain regions of an animal model of depression, the Wistar-Kyoto (WKY) rat. Both nuclear receptors have been implicated in the development or treatment of depression. The expression of nuclear orphan receptor-1 (Nor-1), a member of the NR4A nuclear orphan receptor family, is induced by electroconvulsive shock, an effective treatment for depression. Deficit in the levels or function of the glucocorticoid receptor (GR) found in depressed patients has been causally implicated in depression, as this deficit is normalized by antidepressant treatments. Baseline levels of amygdalar Nor-1 and GR mRNA were higher in the WKYs compared to the comparison control Sprague-Dawley rats (SD). Prolonged treatment with the antidepressant desipramine (DMI) decreased the expression of both transcripts in the WKY strain concomitantly with decreased immobility in the forced swim test (FST) of depressive behavior. Using short hairpin RNA (shRNA) targeted against Nor-1, we investigated the direct contribution of elevated Nor-1 expression in the amygdala of WKY to their exaggerated depressive behavior in the FST. After validating the shRNA targeting of Nor-1 in vitro, Nor-1 shRNA containing vector was infused intracerebroventricularly, using a linear polyethylenimine (PEI)-containing in vivo gene delivery system. Repeated administration of Nor-1 shRNA ameliorated the depressive behavior of WKYs in the FST and decreased amygdalar Nor-1 mRNA levels without affecting GR mRNA levels. These data demonstrate that brain region-specific changes in GR expression in response to DMI are strain dependent and that elevated amygdalar Nor-1 expression can contribute to depressive behavior in the WKY model of depression.",
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