β-Amyloid (Aβ) peptide is a characteristic feature of Alzheimer’s disease (AD) and accumulation of Aβ is associated with loss of synaptic plasticity and neuronal cell death. Aggregation of Aβ initiates numerous molecular signalling pathways leading to oxidative stress, mitochondrial dysfunction as well as an imbalance of calcium ion influx homeostasis. Recently, it has been shown that transient receptor potential melastatin 2 (TRPM2), a non-selective calcium-permeable cation channel has been postulated to play a vital role in the neuronal death, indicating the potential of TRPM2 inhibition in CNS disease. In this study, neuroprotective potential of 2-aminoethoxydiphenyl borate (2-APB), a broad-spectrum calcium channels blocker was investigated in Aβ-induced memory deficits in rats. In addition, effect of 2-APB on TRPM2 channels gene and protein expressions and also on calcium and memory related proteins was investigated in the hippocampus. Intracerebroventricular (I.C.V.) administration of Aβ (Aβ_25–35, 10 μg) markedly induced cognitive impairment and upregulation of mRNA and protein expression of TRPM2 in the hippocampus. In addition, AChE activity was also increased in the cortex of the Aβ administered animals. Three-week treatment with 2-APB led to the down-regulation of TRPM2 mRNA and protein expression in the hippocampus and also improved the cognitive functions which was evident from the behavioral parameters. Moreover, 2-APB treatment also increased the calcium and memory associated proteins namely p-CaMKII, p-GSK-3β, p-CREB and PSD-95 in the hippocampus and reduced the mRNA level of calcium buffering proteins and calcineurin A (PPP3CA) in the hippocampus. Furthermore, 2-APB treatment significantly reduced the AChE activity in the cortex. Thus, our findings suggest the neuroprotective effect of 2-APB in Aβ-induced cognitive impairment.

β-淀粉样蛋白 (Aβ) 肽是阿尔茨海默病 (AD) 的特征，Aβ 的积累与突触可塑性丧失和神经元细胞死亡有关。Aβ 的聚集引发了许多分子信号通路，导致氧化应激、线粒体功能障碍以及钙离子内流稳态失衡。最近，已经表明瞬时受体电位 melastatin 2 (TRPM2)，一种非选择性钙渗透性阳离子通道，在神经元死亡中起重要作用，表明 TRPM2 抑制在 CNS 疾病中的潜力。在这项研究中，研究了广谱钙通道阻滞剂 2-氨基乙氧基硼酸二苯酯 (2-APB) 在 Aβ 诱导的大鼠记忆缺陷中的神经保护作用。此外，在海马中研究了 2-APB 对 TRPM2 通道基因和蛋白质表达以及钙和记忆相关蛋白的影响。脑室内 (ICV) 给予 Aβ (Aβ_25–35,10 μg) 显着诱导认知障碍和海马中 TRPM2 的 mRNA 和蛋白表达上调。此外，Aβ 给药动物的皮质中 AChE 活性也增加。三周的 2-APB 治疗导致海马中 TRPM2 mRNA 和蛋白质表达的下调，并且还改善了认知功能，这从行为参数中可以看出。此外，2-APB 治疗还增加了海马中的钙和记忆相关蛋白，即 p-CaMKII、p-GSK-3β、p-CREB ​​和 PSD-95，并降低了钙缓冲蛋白和钙调磷酸酶 A (PPP3CA) 的 mRNA 水平在海马体中。此外，2-APB 处理显着降低了皮质中的 AChE 活性。因此，我们的研究结果表明 2-APB 在 Aβ 诱导的认知障碍中的神经保护作用。