Norepinephrine alters the expression of genes involved in neuronal sprouting and differentiation: Relevance for major depression and antidepressant mechanisms

Daphna Laifenfeld, Ehud Klein, Dorit Ben-Shachar

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Recent research into depression has focused on the involvement of long-term intracellular processes, leading to abnormal neuronal plasticity in brains of depressed patients, and reversed by antidepressant treatment. Given a suggested decrease in noradrenergic transmission in depression, and an antidepressant induced increase in norepinephrine (NE) level, a possible role for NE in mediating alterations in neuronal morphology and plasticity was examined. Human neuroblastoma SH-SY5Y cells treated with 10-5 M NE presented an elongated granule-rich cell-body and increased number of neurites, when compared with non-treated cells. Moreover, cell survival was enhanced in the presence of NE, while proliferation was inhibited. The above effects suggest a role for NE in cell differentiation. Indeed similar effects on cell survival and neurite outgrowth were induced in SH-SY5Y cells by retinoic acid (RA), an established differentiating agent. Finally, NE treatment resulted in a progressive decrease in the pluripotent marker Oct4 and an increase in the neuronal growth cone marker, growth-associated-protein 43 (GAP-43). Along-side these effects, NE-treated cells presented alterations in the expression of 44 genes as observed in a neurobiology cDNA microarray. Among the altered genes, an increase in the expression level of two neurite-outgrowth promoting genes, neural cell adhesion molecule L1 and laminin, was confirmed by RT-PCR. Taken together, the results support a role for NE in processes of synaptic connectivity, and may point to a role for this neurotransmitter in mediating the suggested neuronal plasticity in depression and in antidepressant treatment.

Original languageEnglish
Pages (from-to)1054-1064
Number of pages11
JournalJournal of Neurochemistry
Volume83
Issue number5
DOIs
StatePublished - Dec 2002
Externally publishedYes

Keywords

  • Depression
  • Differentiation
  • GAP-43
  • Laminin
  • Neural cell adhesion L1
  • Norepinephrine

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