Naringin enhances long-term potentiation and recovers learning and memory deficits of amyloid-beta induced Alzheimer’s disease-like behavioral rat model

柚皮苷 莫里斯水上航行任务 长时程增强 海马体 海马结构 神经科学 神经保护 奶油 阿尔茨海默病 β淀粉样蛋白 化学 药理学 心理学 医学 内科学 生物化学 受体 基因 转录因子 疾病 色谱法
作者
Ga-Young Choi,Hyun-Bum Kim,Eun‐Sang Hwang,Ho-Sub Park,Jae-Min Cho,Young-Ki Ham,Jin Hee Kim,Mi-Kyung Mun,Sungho Maeng,Ji Ho Park
出处
期刊:Neurotoxicology [Elsevier]
卷期号:95: 35-45 被引量:20
标识
DOI:10.1016/j.neuro.2022.12.007
摘要

Alzheimer's disease (AD), as the most typical type of dementia, is a chronic neurodegenerative disorder characterized by progressive learning and memory impairment. It is known that the main causes of AD are the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Naringin is a flavonoid from citrus fruits, especially in grapefruit, which has anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. However, the effect of naringin in AD caused by Aβ has not been clearly studied, and there are few studies on the electrophysiological aspect. Thus, we investigated the ex vivo neuroprotective effect of naringin through the long-term potentiation (LTP) on organotypic hippocampal slice cultures. We evaluated the in vivo effects of naringin (100 mg/kg/day) orally treated for 20 days on learning, memory, and cognition which was impaired by bilateral CA1 subregion injection of Aβ. Cognitive behaviors were measured 2 weeks after Aβ injection using behavioral tests and the hippocampal expression of apoptotic and neurotrophic regulators were measured by immunoblotting. In hippocampal tissue slices, naringin dose-dependently increased the field excitatory postsynaptic potential (fEPSP) after theta burst stimulation and attenuated Aβ-induced blockade of fEPSP in the hippocampal CA1 area. In Aβ injected rats, naringin improved object recognition memory in the novel object test, avoidance memory in the passive avoidance test and spatial recognition memory in the Morris water maze test. In the hippocampus, naringin attenuated the Aβ-induced cyclooxygenase-2, Bax activation and Bcl-2, CREB, BDNF and TrkB inhibition. These results suggest that naringin has therapeutic potential to reduce neuronal inflammation and apoptosis induced by Aβ related with the BDNF/TrkB/CREB signaling.
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