Noradrenaline increases neural precursor cells derived from adult rat dentate gyrus through beta2 receptor

Abstract

Several preclinical researches indicate that increased neurogenesis in the adult hippocampus might underlie the therapeutic effect of antidepressant treatment. Most antidepressant drugs have ability to increase serotonin (5-HT) and/or noradrenaline (NA) in brain, and chronic treatment with antidepressant drugs increases the number of proliferating neural precursor cells and neurogenesis in hippocampus. However, the direct effects of antidepressant drugs, 5-HT and NA on the neural precursor cells remain largely unknown. Neural precursor cells in adult hippocampus are divided into stem/progenitor cells of four types based on stages of neural development. We recently established a culture system of adult rat dentate gyrus-derived neural precursor cells (ADPs), which correspond to be type 2a early progenitor cells. Here the direct effects of antidepressant drugs of four types (fluoxetine, imipramine, reboxetine, and tranylcypromine) and two neurotransmitters (5-HT and NA) on the proliferation of ADPs were investigated. Neither antidepressant drugs of all types nor 5-HT increased the number of ADPs. On the other hand, NA increased the number and the DNA synthesis of ADPs. The effect of NA on ADP proliferation was antagonized by propranolol and timolol (β-adrenergic receptor (AR) antagonists), but not by phentolamine (α-AR antagonist), prazosin (α1-AR antagonist), or yohimbine (α2-AR antagonist). Moreover, it was antagonized by ICI 118, 551 (β2-AR selective antagonist) and salmeterol (β2-AR selective agonist) promoted ADP proliferation. These results suggest that NA might increase the proliferation of early progenitor cells in adult hippocampus via β2-AR directly, but antidepressant drugs and 5-HT do not.