背景:阿尔茨海默病(AD)影响大脑并导致认知和情绪困难。目前,没有可行的治疗方法来阻止或减缓AD的进展。金属硫蛋白III(MT-III)具有抗氧化和抗炎特性,表明可能的治疗益处。本研究旨在探讨MT-III对AD病理改变和认知能力的影响。
方法:在这项研究中,我们采用普遍接受的AD小鼠模型(3xTg-AD)作为测试受试者,并给予载体或MT-III。对小鼠进行Morris水迷宫测试以评估其空间学习和记忆能力。此外,为了评估对海马神经元群的后续影响,Nissl染色和神经元核抗原(NeuN)免疫组织化学用于鉴定细胞形态变化和密度。免疫组织化学还用于检测β-淀粉样蛋白(Aβ)和神经胶质纤维酸性蛋白(GFAP),以测量Aβ的积累和星形胶质细胞的生长。Westernblot也用于测量Tau病理相关的PHD指蛋白1(PHF-1),磷酸化Tau(AT-8),和总Tau蛋白。
结果:MT-III的给药显著增强了3xTg-AD小鼠的空间学习和记忆功能,如Morris水迷宫试验所证明的(p<0.01)。根据免疫组织化学和获得的发现,观察到用MT-III处理的小鼠的脑组织显示Nissl体和NeuN强度显着增加(p<0.01),而Aβ积累和GFAP显着降低(p<0.01)。此外,MT-III大大降低了Tau磷酸化相关的PHF-1和AT-8的水平(p<0.01),并略微降低了Tau5的水平(p<0.05)。
结论:总之,我们的研究表明,MT-III有能力改善AD小鼠模型的病理改变,并保护其认知和情绪能力.通过减少β-淀粉样蛋白的积累和降低Tau病理的强度,MT-III保护海马亚区神经元免受病理伤害。此外,MT-III通过抑制星形胶质细胞的异常增殖来减轻炎症。最重要的是,MT-III极大地增强了小鼠与空间学习和记忆相关的认知能力,表明其对AD的有希望的治疗特性。
BACKGROUND: Alzheimer\'s disease (AD) affects the brain and causes difficulties with cognition and emotions. At present, there are no viable therapies to halt or slow down the advancement of AD. Metallothionein III (MT-III) exhibits antioxidant and anti-inflammatory characteristics, indicating possible therapeutic benefits. This study aimed to explore the influence of MT-III on AD pathological alterations and cognitive abilities.
METHODS: In this research, we employed the universally accepted AD mouse models (3xTg-AD) as test subjects and administrated vehicle or MT-III. The mice were subjected to the Morris water maze test to assess their spatial learning and memory capabilities. Moreover, to evaluate the consequent effects on neuronal groups in the hippocampus, the Nissl staining and neuronal nuclear antigen (NeuN) immunohistochemistry were used to identify the cellular morphology changes and density. Immunohistochemistry was also used to detect β-amyloid (Aβ) and glial fibrillary acidic protein (GFAP) to measure Aβ accumulation and astrocyte growth. Western blot was also used to measure Tau pathology-related PHD finger protein 1 (PHF-1), phosphorylated Tau (AT-8), and total Tau protein.
RESULTS: The administration of MT-III notably enhanced spatial learning and memory function in 3xTg-AD mice, as evidenced by the Morris water maze test (p < 0.01). According to immunohistochemistry and the obtained findings, it was observed that brain tissues of mice treated with MT-III showed a notable increase of Nissl bodies and NeuN intensity (p < 0.01) while a remarkable decrease in Aβ accumulation and GFAP (p < 0.01). Additionally, MT-III largely decreased levels of Tau phosphorylation-related PHF-1 and AT-8 (p < 0.01) and slightly reduced the level of Tau 5 (p < 0.05).
CONCLUSIONS: In summary, our research indicates that MT-III has the capacity to ameliorate pathological alterations in AD mouse models and safeguard their cognitive and emotional abilities. By decreasing β-amyloid accumulation and reducing the intensity of Tau pathology, MT-III protected hippocampal subfield neurons against pathological harm. Furthermore, MT-III reduced inflammation by inhibiting abnormal proliferation of astrocytes. Of utmost importance, MT-III greatly enhanced the cognitive abilities related to spatial learning and memory in mice, suggesting its promising therapeutic properties for AD.