Antidepressants and prolonged stress in rats modulate CAM-L1, laminin, and pCREB, implicated in neuronal plasticity

D. Laifenfeld, R. Karry, E. Grauer, E. Klein, D. Ben-Shachar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Previously, we reported an ability of NE to promote processes of plasticity in neuroblastoma cells, as observed by morphological changes such as an elongated granule-rich cell body and neuritegenesis, in addition to a progressive decrease in the pluripotent marker Oct4 and an increase in the growth cone marker GAP-43. This was accompanied by the induction of three plasticity genes forming a functional cluster, the cell adhesion molecule L1 (CAM-L1), laminin, and CREB, all involved in neuronal plasticity and neurite outgrowth. In the present study, we hypothesized that the regulation of CAM-L1, laminin, and CREB/pCREB by NE could mediate processes of plasticity in the mode of action of antidepressants, as well as in the long-term effects of stress, in rats, given the association of both with NE alterations and neuronal plasticity. In the first experiment, rats were chronically administered with antidepressants (21 days). In the second experiment, rats were exposed to chronic stress and examined 4 months later, a model shown to exhibit behavioral indices of stress. We found brain region-specific alterations in mRNA and protein levels of CAM-L1, laminin, and pCREB in rats chronically treated with the noradrenergic antidepressant desipramine and, to a lesser extent, in those treated with fluoxetine. Stressed rats presented a decrease in CAM-L1, laminin, and pCREB, specifically in brain areas implicated in stress. Our findings suggest that noradrenergic-regulated plasticity genes such as CAM-L1, laminin, and CREB play an important role both in stress and in the treatment of depression.

Original languageEnglish
Pages (from-to)432-441
Number of pages10
JournalNeurobiology of Disease
Volume20
Issue number2
DOIs
StatePublished - Nov 2005
Externally publishedYes

Funding

FundersFunder number
Chief Scientist Israel Ministry of Health
Rambam Medical Center Research and Development Fund

    Keywords

    • Antidepressants
    • CAM-L1
    • CREB/pCREB
    • Laminin
    • Neuronal plasticity
    • Stress

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