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Novel Phenylethanoid Glycosides Improve Hippocampal Synaptic Plasticity via the Cyclic Adenosine Monophosphate-CREB-Brain-Derived Neurotrophic Growth Factor Pathway in APP/PS1 Transgenic Mice.
Ji, Shiliang; Wu, Yijie; Zhu, Ruifang; Guo, Dongkai; Jiang, Yiguo; Huang, Lifeng; Ma, Xinwei; Yu, Liqiang.
Afiliação
  • Ji S; Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China, dg21300014@smail.nju.edu.cn.
  • Wu Y; Department of Neurology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
  • Zhu R; Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
  • Guo D; Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
  • Jiang Y; Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
  • Huang L; Department of Pharmacy, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
  • Ma X; Department of Medical Imaging, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
  • Yu L; Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Gerontology ; 69(9): 1065-1075, 2023.
Article em En | MEDLINE | ID: mdl-37285833
INTRODUCTION: Alzheimer's disease (AD) is a major public health concern worldwide, but there are still no drugs available that treat it effectively. Previous studies have shown that phenylethanoid glycosides have pharmacological effects, which include anti-AD properties, but the underlying mechanisms by which they ameliorate AD symptoms remain unknown. METHODS: In this study, we used an APP/PS1 AD mouse model to explore the function and mechanisms underlying savatiside A (SA) and torenoside B (TB) in the treatment of AD. SA or TB (100 mg·kg-1·d-1) was orally administered to 7-month-old APP/PS1 mice for 4 weeks. Cognitive and memory functions were measured using behavioral experiments (including the Morris water maze test and the Y-maze spontaneous alternation test). Molecular biology experiments (including Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays) were used to detect any corresponding changes in signaling pathways. RESULTS: The results showed that SA or TB treatment could significantly reduce cognitive impairment in APP/PS1 mice. We also showed that chronic treatment with SA/TB could prevent spine loss, synaptophysin immunoreactivity, and neuronal loss in mice, thereby improving synaptic plasticity and moderating learning and memory deficits. SA/TB administration also promoted the expression of synaptic proteins in APP/PS1 mouse brains and upregulated phosphorylation of proteins in the cyclic adenosine monophosphate (cAMP)/CREB/brain-derived neurotrophic growth factor (BDNF) pathway that are responsible for synaptic plasticity. Additionally, chronic SA/TB treatment increased the levels of BDNF and nerve growth factor (NGF) in the brains of APP/PS1 mice. Both astrocyte and microglia volumes, as well as the generation of amyloid ß, were also decreased in SA/TB-treated APP/PS1 mice compared to control APP/PS1 mice. CONCLUSION: In summary, SA/TB treatment was associated with activation of the cAMP/CREB/BDNF pathway and increased BDNF and NGF expression, indicating that SA/TB improves cognitive functioning via nerve regeneration. SA/TB is a promising candidate drug for the treatment of AD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos beta-Amiloides / Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos beta-Amiloides / Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article