Premium
Norepinephrine alters the expression of genes involved in neuronal sprouting and differentiation: relevance for major depression and antidepressant mechanisms
Author(s) -
Laifenfeld Daphna,
Klein Ehud,
BenShachar Dorit
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01215.x
Subject(s) - neurite , biology , antidepressant , monoamine neurotransmitter , microbiology and biotechnology , neuroplasticity , neuroblast , growth cone , neural stem cell , cellular differentiation , neuroscience , stem cell , neurogenesis , serotonin , hippocampus , gene , axon , receptor , biochemistry , in vitro
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). Alongside 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.