Adrenergic β receptor activation prevents human soluble amyloid β (Aβ)-induced impairment of long-term potentiation (LTP) in slices. On the basis of the evidence that human Aβ_1–42-induced impairment of LTP is due to Aβ_1–42-mediated Zn²⁺ toxicity, we postulated that adrenergic β receptor activation reduces Aβ_1–42-mediated intracellular Zn²⁺ toxicity followed by rescuing Aβ_1–42 toxicity. To test the effect of adrenergic β receptor activation, LTP was recorded at perforant pathway-dentate granule cell synapses of anesthetized rats 60 min after Aβ_1–42 injection into the dentate granule cell layer. Human Aβ_1–42-induced impairment of LTP was rescued by co-injection of isoproterenol, an adrenergic β receptor agonist, but not by co-injection of phenylephrine, an adrenergic α₁ receptor agonist. Isoproterenol did not reduce Aβ_1–42 uptake into dentate granule cells, but reduced increase in intracellular Zn²⁺ in dentate granule cells induced by Aβ_1–42. In contrast, phenylephrine did not reduce both Aβ_1–42 uptake and increase in intracellular Zn²⁺ by Aβ_1–42. In the case of human Aβ₁₋₄₀ and rat Aβ_1–42, which do not increase intracellular Zn²⁺, human Aβ₁₋₄₀- and rat Aβ_1–42-induced impairments of LTP were not rescued by co-injection of isoproterenol. The present study indicates that adrenergic β receptor activation reduces Aβ_1–42-mediated increase in intracellular Zn²⁺ in dentate granule cells, resulting in rescuing Aβ_1–42-induced impairment of LTP. It is likely that noradrenergic neuron activation by stimulating the locus coeruleus is effective for rescuing Aβ_1–42-induced cognitive decline that is caused by intracellular Zn²⁺ dysregulation in the hippocampus.

肾上腺素β受体激活可防止人类可溶性淀粉样β（Aβ）引起的片中长期增强（LTP）损伤。根据证据表明人类_Aβ1–42诱导的LTP损伤是由于_Aβ1–42介导的Zn ²⁺毒性所致，我们推测肾上腺素β受体激活会降低_Aβ1–42介导的细胞内Zn ²⁺毒性然后抢救_Aβ1–42毒性。为了测试肾上腺素β受体激活的作用，在将_Aβ1–42注入齿状颗粒细胞层后60分钟，在麻醉大鼠的穿孔途径-齿状颗粒细胞突触中记录LTP 。人_Aβ1–42LTP的诱导损伤是由异丙肾上腺素的共注射，肾上腺素能β受体激动剂，但不是由去氧肾上腺素的共注射，肾上腺素能α救出₁受体激动剂。异丙肾上腺素不会减少齿状颗粒细胞对_Aβ1–42的摄取，但会减少由_Aβ1–42诱导的齿状颗粒细胞中细胞内Zn ^2+的增加。相比之下，去氧肾上腺素并没有减少Aβ两者_1-42摄取和增加细胞内锌²⁺由Aβ _1-42。对于不增加细胞内Zn ²⁺的人_Aβ1−40和大鼠_Aβ1–42，人_Aβ1−40-和大鼠Aβ共注射异丙肾上腺素不能挽救_1–42引起的LTP损伤。本研究表明，肾上腺素能β受体的活化减少了齿状颗粒细胞中_Aβ1–42介导的细胞内Zn ^2+的增加，从而挽救了_Aβ1–42诱导的LTP损伤。通过刺激蓝斑轨迹来激活去甲肾上腺素能神经元对于挽救_Aβ1–42引起的认知衰退是有效的，这是由海马中细胞内Zn ²⁺失调引起的。