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Isoniazid improves cognitive performance, clears Aß plaques, and protects dendritic synapses in APP/PS1 transgenic mice.
Chen, Jiacheng; Guo, Ning; Ruan, Yuting; Mai, Yingren; Liao, Wang; Feng, Yanqing.
Afiliação
  • Chen J; Department of Neurology, National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Guangzhou, China.
  • Guo N; Department of Neurosurgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • Ruan Y; Department of Rehabilitation, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Mai Y; Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Liao W; Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Feng Y; Department of Neurology, National Key Clinical Department, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Guangzhou, China.
Front Aging Neurosci ; 15: 1105095, 2023.
Article em En | MEDLINE | ID: mdl-36743440
Background and objective: Alzheimer's disease (AD) is characterized by amyloid ß (Aß) aggregation and neuroinflammation. This study aimed to investigate the therapeutic effect of isoniazid (INH) against AD. Methods: The APP/PS1 transgenic mouse model of AD was adopted. The APP/PS1 mice received oral INH (45 mg/kg/d) for 14 days. The cognitive capability was assessed by the Morris Water Maze test. Amyloid plaques and Aß levels were determined by immunohistochemistry and ELISA assay. The dendritic spines were analyzed by DiOlistic labeling. Immunofluorescence staining was used to observe the microglia and astrocytes. Results: The Morris Water Maze test suggested that INH administration can effectively attenuate the reference memory deficit and improve the working memory of the APP/PS1 mice compared to the untreated mice (all p < 0.001). INH significantly decreased the Aß plaques in the hippocampus and cortex and reduced the levels of Aß1-40 and Aß1-42 in the brain homogenates, cerebrospinal fluid, and serum (all p < 0.001). INH also inhibited enzyme activities of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1, p < 0.05) and monoamine oxidase B (Mao-b, p < 0.01). INH significantly increased the protrusion density in the hippocampus (p < 0.01). Immunofluorescence staining revealed that INH significantly reduced the number of activated microglia and astrocytes around the Aß plaques (both p < 0.01). Conclusion: Isoniazid administration effectively improved cognitive performance, cleared Aß plaques, protected dendritic synapses, and reduced innate immune cells around the Aß plaques, suggesting that INH could be a potential drug for AD treatment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article