Isoproterenol, an adrenergic β receptor agonist, induces metallothionein synthesis followed by canceling amyloid β1-42-induced neurodegeneration.

Abstract

Adrenergic β receptor activation may ameliorate amyloid β toxicity. We examined whether isoproterenol, an adrenergic β receptor agonist reduces neurodegeneration caused by Aβ1-42, for which intracellular Zn2+ dysregulation is a trigger. Neurodegeneration was assessed in the dentate granule cell layer 14days after intracerebroventricular injection of human Aβ1-42 into the mouse brain. Neurodegeneration was canceled after co-injection of isoproterenol. Isoproterenol did not affect Aβ staining (uptake) in the dentate granule cell layer 1h after Aβ injection. In contrast, isoproterenol reduced intracellular Zn2+ level increased by Aβ. The synthesis of intracellular metallothioneins (MTs), Zn2+-binding proteins was not enhanced in the dentate granule cell layer 24h after Aβ1-42 injection, but significantly enhanced after co-injection of isoproterenol. These data indicate that isoproterenol enhances MT synthesis and cancels neurodegeneration via intracellular Zn2+ toxicity after Aβ1-42 injection. It is likely that MT synthesis enhanced by adrenergic β receptor-mediated signaling contributes to ameliorating Aβ1-42 toxicity in the brain.