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 14 days 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 1 h 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 24 h 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.
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Planned experiments: AT Performed the Experiments: YK, KT, and ME Analyzed data: HT, YK, KT, and ME Wrote the paper: AT All authors reviewed the manuscript.
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Kawano, Y., Tamura, K., Egawa, M. et al. Isoproterenol, an adrenergic β receptor agonist, induces metallothionein synthesis followed by canceling amyloid β1-42-induced neurodegeneration. Biometals 35, 303–312 (2022). https://doi.org/10.1007/s10534-022-00365-w
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DOI: https://doi.org/10.1007/s10534-022-00365-w