Liraglutide Ameliorates Hyperhomocysteinemia-Induced Alzheimer-Like Pathology and Memory Deficits in Rats via Multi-molecular Targeting

• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2019,（4）
• 页码范围: 724-734
• 页数: 11页
• 语种: 英文

摘要

Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD),and insulinresistance is commonly seen in patients with Hhcy.Liraglutide (Lir),a glucagon-like peptide that increases the secretion and sensitivity of insulin,has a neurotrophic or neuroprotective effect.However,it is not known whether Lir ameliorates the AD-like pathology and memory deficit induced by Hhcy.By vena caudalis injection of homocysteine to produce the Hhcy model in rats,we found here that simultaneous administration of Lir for 2 weeks ameliorated the Hhcy-induced memory deficit,along with increased density of dendritic spines and up-regulation of synaptic proteins.Lir also attenuated the Hhcy-induced tau hyperphosphorylation and Aβ overproduction,and the molecular mechanisms involved the restoration of protein phosphatase-2A activity and inhibition of β-and γ-secretases.Phosphorylated insulin receptor substrate-1 also decreased after treatment with Lir.Our data reveal that Lir improves the Hhcy-induced AD-like spatial memory deficit and the mechanisms involve the modulation of insulin-resistance and the pathways generating abnormal tau and Aβ.