Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
Laboratory of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
Biochem Biophys Res Commun. 2020 Jul 12;528(1):174-178. doi: 10.1016/j.bbrc.2020.04.046. Epub 2020 May 29.
Oxytocin, a peptide hormone synthesized in the hypothalamic paraventricular nucleus, has been reported to participate in the regulation of learning and memory performance. However, no report has demonstrated the effect of oxytocin on the amyloid-beta (Aβ)-induced impairment of synaptic plasticity. In this study, we examined the effects of oxytocin on the Aβ-induced impairment of synaptic plasticity in mice.
To investigate the effect of oxytocin on synaptic plasticity, we prepared acute hippocampal slices for extracellular recording and assessed long-term potentiation (LTP) with perfusion of the Aβ active fragment (Aβ) in the absence and presence of oxytocin.
We found that oxytocin reversed the impairment of LTP induced by Aβ perfusion in the mouse hippocampus. These effects were blocked by pretreatment with the selective oxytocin receptor antagonist L-368,899. Furthermore, the treatment with the ERK inhibitor U0126 and selective Ca-permeable AMPA receptor antagonist NASPM completely antagonized the effects of oxytocin.
This is the first report to demonstrate that oxytocin could reverse the effects of Aβ on hippocampal LTP in mice. We propose that ERK phosphorylation and Ca-permeable AMPA receptors are involved in this effect of oxytocin.
催产素是一种在下丘脑室旁核合成的肽类激素，据报道它参与了学习和记忆表现的调节。然而，目前尚无报道表明催产素对淀粉样β（Aβ）诱导的突触可塑性损伤有影响。在本研究中，我们研究了催产素对小鼠 Aβ诱导的突触可塑性损伤的影响。
为了研究催产素对突触可塑性的影响，我们制备了急性海马脑片进行细胞外记录，并在不存在和存在催产素的情况下评估 Aβ 活性片段（Aβ）灌流引起的长时程增强（LTP）。
我们发现催产素逆转了 Aβ 灌流诱导的小鼠海马 LTP 损伤。这些作用可被选择性催产素受体拮抗剂 L-368,899 预处理阻断。此外，用 ERK 抑制剂 U0126 和选择性钙通透型 AMPA 受体拮抗剂 NASPM 处理可完全拮抗催产素的作用。
这是第一项表明催产素可以逆转 Aβ 对小鼠海马 LTP 影响的研究报告。我们提出 ERK 磷酸化和钙通透型 AMPA 受体参与了这种催产素作用。
