Original Article

Neuropsychopharmacology (2006) 31, 1165–1176. doi:10.1038/sj.npp.1300924; published online 5 October 2005

Preclinical Research

Cell Proliferation is Influenced by Bulbectomy and Normalized by Imipramine Treatment in a Region-Specific Manner

Gerburg Keilhoff1, Axel Becker2, Gisela Grecksch2, Hans-Gert Bernstein3 and Gerald Wolf1

  1. 1Institute of Medical Neurobiology, University of Magdeburg, Magdeburg, Germany
  2. 2Institute of Pharmacology and Toxicology, University of Magdeburg, Magdeburg, Germany
  3. 3Department of Psychiatry, University of Magdeburg, Magdeburg, Germany

Correspondence: Dr G Keilhoff, Institute of Medical Neurobiology, University of Magdeburg, Leipziger Strasse 44, Magdeburg D-39120, Germany. Tel: +49 391 67 14368; Fax: +49 391 67 14365; E-mail: gerburg.keilhoff@medizin.uni-magdeburg.de

Received 25 April 2005; Revised 16 August 2005; Accepted 30 August 2005; Published online 5 October 2005.

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Abstract

Growing evidence indicates that alterations of neuroplasticity may contribute to the pathophysiology of depression. In contrast, various antidepressants increase adult hippocampal neurogenesis and block the effects of stress. These findings result in the 'neurogenesis hypothesis of depression'. The present study seeks to determine out whether cell proliferation is altered in the hippocampus, subventricular zone (SVZ), and basolateral amygdala of adult rats exposed to bilateral olfactory bulbectomy, another established model of depression and, if so, how imipramine effects bulbectomy-induced changes of cell genesis. Bulbectomy results in a significant reduction of cell proliferation in the hippocampus and SVZ, an effect that is normalized by subchronic doses of imipramine. Moreover, an increase in cell genesis in the basolateral amygdala, which is not affected by imipramine, is demonstrated. TUNEL staining indicates an enhanced apoptosis after bulbectomy in the SVZ that cannot be reduced by imipramine. Cell death rates in the hippocampus and amygdala are not affected by bulbectomy. The opposing effects of bulbectomy and imipramine treatment in the hippocampus and amygdala demonstrate that these structures of the limbic system, both integrated in emotional processing, react quite differently with regard to neuroplasticity. Further to this, we discuss a possible link between the pathogenesis of depression and changed neuronal plasticity in the SVZ.

Keywords:

amygdala, bulbectomy, depression, hippocampus, rat, subventricular zone

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