N'Go Pacôme Kouadio, Ahami Omar Touhami Ahmed, El Hessni Aboubaker, Azzaoui Fatima-Zahra, Aboussaleh Youssef, Tako Antoine Némé
Peleforo GON COULIBALY University, Training and Research Unit of Biological Sciences, Department of Animal Biology, PO Box 1328, Korhogo, Ivory Coast.
Clinical and Cognitive Neurosciences Group, Biology and Health Lab, Ibn Tofail University, PO Box 133, Kenitra, Morocco.
Transl Neurosci. 2021 Dec 16;12(1):545-560. doi: 10.1515/tnsci-2020-0183. eCollection 2021 Jan 1.
Alzheimer's disease (AD) is a threatening disease for African populations in the upcoming years because of the increase in their expectancy of life. Here, we investigated whether natural products from as catechin and two dimeric procyanidins (catechin + hexose) could prevent progression of oxidative stress and cognitive changes using an AD-like rat model induced by Aβ injection into the hippocampal CA1 subfield.
Adult male Wistar rats were either microinjected with 1% ammonia as a vehicle (10 µL) or aggregated Aβ at 10 µg bilateral hippocampus. On the 14th day of post-surgery, some Aβ rats were treated with melatonin (10 mg/kg i.p.) or with the extract (300 mg/kg p.o.), and some sham-operated rats received the extract alone. Cognitive abilities were tested with Y-maze, object recognition test and Morris Water Maze. Oxidative stress markers as well as the level of activated microglial cells were assayed in the brain.
Aβ rats exhibited significant deficits of recognition memory and spatial learning. This was associated with an increase of microglia Iba 1 immunoreactivity as well as nitric oxide (NO), malondialdehyde and superoxide dismutase levels but not to the thiol content in the hippocampus, prefrontal cortex and septum of AD-like rats. The extract treatment mitigated Aβ-induced cognitive impairments and reversed microglia overactivation and subsequent generation of oxidative stress markers. Interestingly, the neuroprotective actions of the extract seem to be comparable to the control drug melatonin used albeit with some more beneficial effects.
These findings are preliminary and should be strengthened by more pharmacological studies of bioactive compounds of before being proposed as a promising drug against AD.
由于非洲人群预期寿命的增加,阿尔茨海默病(AD)在未来几年对他们构成了一种威胁性疾病。在此,我们使用通过向海马CA1亚区注射Aβ诱导的类AD大鼠模型,研究了儿茶素和两种二聚体原花青素(儿茶素+己糖)等天然产物是否能够预防氧化应激的进展和认知变化。
成年雄性Wistar大鼠双侧海马分别微量注射1%氨水作为溶剂(10μL)或10μg聚集的Aβ。在手术后第14天,一些Aβ大鼠用褪黑素(10mg/kg腹腔注射)或该提取物(300mg/kg口服)治疗,一些假手术大鼠单独接受该提取物。通过Y迷宫、物体识别测试和莫里斯水迷宫测试认知能力。测定脑中的氧化应激标志物以及活化小胶质细胞的水平。
Aβ大鼠表现出明显的识别记忆和空间学习缺陷。这与小胶质细胞Iba 1免疫反应性增加以及一氧化氮(NO)、丙二醛和超氧化物歧化酶水平升高有关,但与类AD大鼠海马、前额叶皮质和隔区的硫醇含量无关。该提取物治疗减轻了Aβ诱导的认知障碍,并逆转了小胶质细胞过度活化以及随后氧化应激标志物的产生。有趣的是,该提取物的神经保护作用似乎与所用的对照药物褪黑素相当,尽管有一些更有益的效果。
这些发现是初步的,在被提议作为一种有前景的抗AD药物之前,应该通过对该提取物生物活性化合物进行更多的药理学研究来加强。