Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Clin Exp Pharmacol Physiol. 2021 Jun;48(6):877-889. doi: 10.1111/1440-1681.13494. Epub 2021 Mar 29.
Anxiety, hippocampus synaptic plasticity deficit, as well as pro-inflammatory cytokines, are involved in Alzheimer's disease (AD). The present study is designed to evaluate the possible therapeutic effect of crocin on anxiety-like behaviours, hippocampal synaptic plasticity and neuronal shape, as well as pro-inflammatory cytokines in the hippocampus using in vivo amyloid-beta (Aβ) models of AD. The Aβ peptide (1-42) was bilaterally injected into the frontal-cortex. Five hours after the surgery, the rats were given intraperitoneal (IP) crocin (30 mg/kg) daily up to 12 days. Elevated plus maze results showed that crocin treatment after bilateral Aβ injection significantly increased the percentage of spent time into open arms, frequency of entries, and percentage of entries into open arms as compared with the Aβ group. In the open field test, the Aβ+crocin group showed a higher percentage of spent time in the centre and frequency of entries into central zone as compare with the Aβ treated animals. Administering crocin increased the number of soma, dendrites and axonal arbores in the CA1 neurons among the rats with Aβ neurotoxicity. Cresyl violet (CV) staining showed that crocin increased the number of CV-positive cells in the CA1 region of the hippocampus compared with the Aβ group. Silver-nitrate staining indicated that crocin reduced neurofibrillary tangle formation induced by Aβ. Crocin treatment attenuated the expression of TNF-α and IL-1β mRNA in the hippocampus compared with the Aβ group. Our results suggest that crocin attenuated Aβ-induced anxiety-like behaviours and neuronal damage, and synaptic plasticity loss in hippocampal CA1 neurons may via its anti-inflammatory effects.
焦虑、海马突触可塑性缺陷以及促炎细胞因子与阿尔茨海默病（AD）有关。本研究旨在评估藏红花素对体内淀粉样β（Aβ）AD 模型中海马焦虑样行为、海马突触可塑性和神经元形态以及海马内促炎细胞因子的可能治疗作用。将 Aβ 肽（1-42）双侧注入额叶皮质。手术后 5 小时，每天给大鼠腹腔内（IP）注射藏红花素（30mg/kg），持续 12 天。高架十字迷宫结果表明，与 Aβ 组相比，双侧 Aβ 注射后给予藏红花素治疗可显著增加进入开放臂的时间百分比、进入次数和进入开放臂的百分比。在旷场试验中，与 Aβ 处理的动物相比，Aβ+藏红花素组显示出更高的中心时间百分比和进入中央区域的频率。给予藏红花素可增加 Aβ 神经毒性大鼠 CA1 神经元的体、树突和轴突分支数量。硝酸银染色显示，与 Aβ 组相比，藏红花素增加了 CA1 区的 CV 阳性细胞数量。银染色表明，藏红花素可减少 Aβ 诱导的神经原纤维缠结形成。与 Aβ 组相比，藏红花素治疗可减轻海马 TNF-α 和 IL-1β mRNA 的表达。我们的研究结果表明，藏红花素可减轻 Aβ 诱导的焦虑样行为和神经元损伤，并且海马 CA1 神经元的突触可塑性丧失可能与其抗炎作用有关。
