Liraglutide Ameliorates Hyperhomocysteinemia-Induced Alzheimer-Like Pathology and Memory Deficits in Rats via Multi-molecular Targeting
| Autor: | Xiang-Yang Xu, Yao Zhang, Teng Xu, Jun Hu, Shao-Juan Yang, Si Jin, Jian-Zhi Wang, Jia-Zhao Xie |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Hyperhomocysteinemia Pathology medicine.medical_specialty Dendritic spine Homocysteine Physiology medicine.medical_treatment tau Proteins Hippocampus Neuroprotection Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease medicine Animals Phosphorylation Maze Learning Memory Disorders Amyloid beta-Peptides Neuronal Plasticity biology Liraglutide business.industry General Neuroscience Insulin Brain General Medicine medicine.disease Rats Receptors Neurotransmitter Disease Models Animal Insulin receptor Neuroprotective Agents 030104 developmental biology chemistry biology.protein Original Article Insulin Resistance business 030217 neurology & neurosurgery medicine.drug Neurotrophin |
| Zdroj: | Neurosci Bull |
| ISSN: | 1995-8218 1673-7067 |
| DOI: | 10.1007/s12264-018-00336-7 |
| Popis: | Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer’s disease (AD), and insulin-resistance 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. |
| Databáze: | OpenAIRE |
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