title: Protective effects of astragalosides on dexamethasone and Aβ25-35 induced learning and memory impairments due to decrease amyloid precursor protein expression in 12-month male rats.
abstract: Alzheimer's disease (AD) is a chronic neurodegenerative disorder of the elderly characterized by learning and memory impairment. Stress level glucocorticoids (GCs) and β-amyloid (Aβ) peptide deposition are found to be correlated with dementia progression in patients with AD. The astragalosides (AST) was extracted from traditional Chinese herb Astragalus membranaceous. In this study, 12 months male rats were treated with Aβ(25-35) (10 μg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5mg/kg, ig) and AST (8, 16 and 32 mg/kg, ig) or ginsenoside Rg1 (Rg1, 5 mg/kg, ig) for 14 days. We investigated the protective effect of AST against DEX+Aβ(25-35) injury in rats and its mechanisms of action. Our results indicate that DEX+Aβ(25-35) can induce learning and memory impairments and increase APP and Aβ(1-40) expression. AST (16, 32 mg/kg) or Rg1 (5mg/kg) treatment significantly improve learning and memory, down-regulate the mRNA levels of APP and β-secretase, decrease expression of APP and Aβ(1-40) in hippocampus. The results indicated that DEX might increase hippocampal vulnerability to Aβ(25-35) and highlight the potential neuronal protection of AST.
authors.affiliation: Department of Pharmacology, Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Wei-Zu
authors.initials: WZ
authors.lastname: Li
authors.forename: Wang-Yang
authors.initials: WY
authors.lastname: Wu
authors.forename: Da-Ke
authors.initials: DK
authors.lastname: Huang
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Yin
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Kan
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yu-You
authors.initials: YY
authors.lastname: Yao
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Li
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000502:physiology; D000818:Animals; D006690:Bisbenzimidazole; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D004396:Coloring Agents; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology; D007150:Immunohistochemistry; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000523:psychology*; D018696:Neuroprotective Agents; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012503:Saponins / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004396:Coloring Agents; D018076:DNA, Complementary; D005938:Glucocorticoids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012503:Saponins; C074636:amyloid beta-protein (25-35); D003907:Dexamethasone; D006690:Bisbenzimidazole