Department of Physiology, Medical Faculty, Selçuk University, Konya, 42031, Turkey.
Department of Medical Biology, Medical Faculty, KTO Karatay University, Konya, Turkey.
Biol Trace Elem Res. 2022 Sep;200(9):4068-4078. doi: 10.1007/s12011-021-02999-2. Epub 2021 Nov 2.
Alzheimer's disease (AD), especially its sporadic form (sAD), is of multifactorial nature. Brain insulin resistance and disrupted zinc homeostasis are two key aspects of AD that remain to be elucidated. Here, we investigated the effects of dietary zinc deficiency and supplementation on memory, hippocampal synaptic plasticity, and insulin signaling in intracerebroventricular streptozotocin (icv-STZ)-induced sAD in rats. The memory performance was evaluated by Morris water maze. The expression of hippocampal protein and mRNA levels of targets related to synaptic plasticity and insulin pathway was assessed by Western blot and real-time quantitative PCR. We found memory deficits in icv-STZ rats, which were fully recovered by zinc supplementation. Western blot analysis revealed that icv-STZ treatment significantly reduced hippocampal PSD95 and p-GSK3β, and zinc supplementation restored the normal protein levels. mRNA levels of BDNF, PSD95, SIRT1, GLUT4, insulin receptor, and ZnT3 were found to be reduced by icv-STZ and reestablished by zinc supplementation. Our data suggest that zinc supplementation improves cognitive deficits and rescues the decline in key molecular targets of synaptic plasticity and insulin signaling in hippocampus caused by icv-STZ induced sAD in rats.
阿尔茨海默病（AD），特别是其散发性形式（sAD），具有多因素的性质。脑胰岛素抵抗和锌稳态失调是 AD 尚未阐明的两个关键方面。在这里，我们研究了饮食缺锌和补锌对脑室注射链脲佐菌素（icv-STZ）诱导的大鼠散发性 AD 中记忆、海马突触可塑性和胰岛素信号的影响。通过 Morris 水迷宫评估记忆表现。通过 Western blot 和实时定量 PCR 评估与突触可塑性和胰岛素途径相关的海马蛋白和靶标 mRNA 水平的表达。我们发现 icv-STZ 大鼠存在记忆缺陷，补锌可完全恢复。Western blot 分析表明，icv-STZ 处理显著降低了海马 PSD95 和 p-GSK3β，补锌恢复了正常的蛋白水平。BDNF、PSD95、SIRT1、GLUT4、胰岛素受体和 ZnT3 的 mRNA 水平因 icv-STZ 而降低，并通过补锌得以重建。我们的数据表明，补锌可改善认知缺陷，并挽救 icv-STZ 诱导的大鼠散发性 AD 中海马中突触可塑性和胰岛素信号关键分子靶标的下降。
