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Dexamethasone and Aβ₂₅-₃₅ accelerate learning and memory impairments due to elevate amyloid precursor protein expression and neuronal apoptosis in 12-month male rats.

Abstract

Alzheimer's disease (AD) is an irreversible, progressive brain disorder of the elderly characterized by learning and memory impairment. Stress level glucocorticoids (GCs) and β-amyloid (Aβ) peptides deposition are found to be correlated with dementia progression in patients with AD. However, little is known about the simultaneous effects of glucocorticoids and Aβ on learning and memory impairment and its mechanism. In this study, 12-month-old male rats were chronically treated with Aβ(25-35) (10 μg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5mg/kg) for 14 days to investigate the effects of DEX and Aβ(25-35) treatment on learning and memory impairments, pathological changes, neuronal ultrastructure, amyloid precursor protein (APP) processing and neuronal cell apoptosis. Our results showed that DEX or Aβ(25-35) treatment alone for 14 days had caused slight damage on learning and memory impairments and hippocampal neurons, but damages were significantly increased with DEX+Aβ(25-35) treatment. And the mRNA levels of the APP, β-secretase and caspase 3 were significantly increased after DEX+Aβ(25-35) treatment. The immunohistochemistry demonstrated that APP, Aβ(1-40), caspase 3 and cytochrome c in hippocampus CA1 were significantly increased. Furthermore, Hoechst 33258 staining and Aβ(1-40) ELISA results showed that DEX+Aβ(25-35) treatment induced hippocampus CA1 neuron apoptosis and increased the level of Aβ(1-40). The results suggest that the simultaneous effects of GCs and Aβ may have important roles in the etiopathogenesis of AD, and demonstrate that stressful life events and GC therapy may increase the toxicity of Aβ and have cumulative impacts on the course of AD development and progression.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Key Laboratory of Chinese Medicine Research and Development, State Administration of Traditional Chinese Medicine, Anhui Medical University, Hefei 230032, PR China.

    , , , , , ,

    Source

    Behavioural brain research 227:1 2012 Feb 01 pg 142-9

    MeSH

    Amyloid Precursor Protein Secretases
    Amyloid beta-Peptides
    Amyloid beta-Protein Precursor
    Analysis of Variance
    Animals
    Apoptosis
    Arabidopsis Proteins
    Caspase 3
    Cytochromes c
    Dexamethasone
    Disease Models, Animal
    Drug Synergism
    Enzyme-Linked Immunosorbent Assay
    Gene Expression Regulation
    Glucocorticoids
    Hippocampus
    Intramolecular Transferases
    Learning Disorders
    Male
    Maze Learning
    Memory Disorders
    Microscopy, Electron, Scanning
    Neurons
    Peptide Fragments
    Rats
    Rats, Sprague-Dawley
    Time Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22061800

    Citation

    Li, Wei-Zu, et al. "Dexamethasone and Aβ₂₅-₃₅ Accelerate Learning and Memory Impairments Due to Elevate Amyloid Precursor Protein Expression and Neuronal Apoptosis in 12-month Male Rats." Behavioural Brain Research, vol. 227, no. 1, 2012, pp. 142-9.
    Li WZ, Li WP, Huang DK, et al. Dexamethasone and Aβ₂₅-₃₅ accelerate learning and memory impairments due to elevate amyloid precursor protein expression and neuronal apoptosis in 12-month male rats. Behav Brain Res. 2012;227(1):142-9.
    Li, W. Z., Li, W. P., Huang, D. K., Kan, H. W., Wang, X., Wu, W. Y., ... Yao, Y. Y. (2012). Dexamethasone and Aβ₂₅-₃₅ accelerate learning and memory impairments due to elevate amyloid precursor protein expression and neuronal apoptosis in 12-month male rats. Behavioural Brain Research, 227(1), pp. 142-9. doi:10.1016/j.bbr.2011.10.038.
    Li WZ, et al. Dexamethasone and Aβ₂₅-₃₅ Accelerate Learning and Memory Impairments Due to Elevate Amyloid Precursor Protein Expression and Neuronal Apoptosis in 12-month Male Rats. Behav Brain Res. 2012 Feb 1;227(1):142-9. PubMed PMID: 22061800.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dexamethasone and Aβ₂₅-₃₅ accelerate learning and memory impairments due to elevate amyloid precursor protein expression and neuronal apoptosis in 12-month male rats. AU - Li,Wei-Zu, AU - Li,Wei-Ping, AU - Huang,Da-Ke, AU - Kan,Hong-Wei, AU - Wang,Xin, AU - Wu,Wang-Yang, AU - Yin,Yan-Yan, AU - Yao,Yu-You, Y1 - 2011/10/29/ PY - 2011/08/09/received PY - 2011/10/18/revised PY - 2011/10/23/accepted PY - 2011/11/9/entrez PY - 2011/11/9/pubmed PY - 2012/4/24/medline SP - 142 EP - 9 JF - Behavioural brain research JO - Behav. Brain Res. VL - 227 IS - 1 N2 - Alzheimer's disease (AD) is an irreversible, progressive brain disorder of the elderly characterized by learning and memory impairment. Stress level glucocorticoids (GCs) and β-amyloid (Aβ) peptides deposition are found to be correlated with dementia progression in patients with AD. However, little is known about the simultaneous effects of glucocorticoids and Aβ on learning and memory impairment and its mechanism. In this study, 12-month-old male rats were chronically treated with Aβ(25-35) (10 μg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5mg/kg) for 14 days to investigate the effects of DEX and Aβ(25-35) treatment on learning and memory impairments, pathological changes, neuronal ultrastructure, amyloid precursor protein (APP) processing and neuronal cell apoptosis. Our results showed that DEX or Aβ(25-35) treatment alone for 14 days had caused slight damage on learning and memory impairments and hippocampal neurons, but damages were significantly increased with DEX+Aβ(25-35) treatment. And the mRNA levels of the APP, β-secretase and caspase 3 were significantly increased after DEX+Aβ(25-35) treatment. The immunohistochemistry demonstrated that APP, Aβ(1-40), caspase 3 and cytochrome c in hippocampus CA1 were significantly increased. Furthermore, Hoechst 33258 staining and Aβ(1-40) ELISA results showed that DEX+Aβ(25-35) treatment induced hippocampus CA1 neuron apoptosis and increased the level of Aβ(1-40). The results suggest that the simultaneous effects of GCs and Aβ may have important roles in the etiopathogenesis of AD, and demonstrate that stressful life events and GC therapy may increase the toxicity of Aβ and have cumulative impacts on the course of AD development and progression. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/22061800/Dexamethasone_and_Aβ₂₅_₃₅_accelerate_learning_and_memory_impairments_due_to_elevate_amyloid_precursor_protein_expression_and_neuronal_apoptosis_in_12_month_male_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(11)00771-6 DB - PRIME DP - Unbound Medicine ER -