Blockage of metallothionein synthesis via adrenaline β receptor activation invalidates dehydroeffusol-mediated prevention of amyloid β1-42 toxicity

Dehydroeffusol, a major phenanthrene in Juncus effusus, protects neurodegeneration induced by intracellular Zn2+ ferried by extracellular amyloid β1-42 (Aβ1-42). Here we focused on adrenaline β receptor activation and the induction of metallothioneins (MTs), intracellular Zn2+-binding proteins to test the protective mechanism of dehydroeffusol. Isoproterenol, an agonist of adrenergic β receptors elevated the level of MTs in the dentate granule cell layer 1 day after intracerebroventricular (ICV) injection. When Aβ1-42 was injected 1 day after isoproterenol injection, pre-injection of isoproterenol protected Aβ1-42 toxicity via reducing the increase in intracellular Zn2+ after ICV injection of Aβ1-42. On the basis of the effect of increased MTs by isoproterenol, dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 2 days. On day later, dehydroeffusol elevated the level of MTs and prevented Aβ1-42 toxicity via reducing Aβ1-42-mediated increase in intracellular Zn2+. In contrast, propranolol, an antagonist of adrenergic β receptors reduced the level of MTs increased by dehydroeffusol, resulting in invalidating the preventive effect of dehydroeffusol on Aβ1-42 toxicity. The present study indicates that blockage of MT synthesis via adrenaline β receptor activation invalidates dehydroeffusol-mediated prevention of Aβ1-42 toxicity. It is likely that MT synthesis via adrenaline β receptor activation is beneficial to neuroprotection and that oral intake of dehydroeffusol preventively serves against the Aβ1-42 toxicity.