Exercise Rehabilitation and/or Astragaloside Attenuate Amyloid-beta Pathology by Reversing BDNF/TrkB Signaling Deficits and Mitochondrial Dysfunction.
Mol Neurobiol
; 59(5): 3091-3109, 2022 May.
Article
em En
| MEDLINE
| ID: mdl-35262870
ABSTRACT
We aim to investigate the mechanisms underlying the beneficial effects of exercise rehabilitation (ER) and/or astragaloside (AST) in counteracting amyloid-beta (Aß) pathology. Aß oligomers were microinjected into the bilateral ventricles to induce Aß neuropathology in rats. Neurobehavioral functions were evaluated. Cortical and hippocampal expressions of both BDNF/TrkB and cathepsin D were determined by the western blotting method. The rat primary cultured cortical neurons were incubated with BDNF and/or AST and ANA12 followed by exposure to aggregated Aß for 24 h. In vivo results showed that ER and/or AST reversed neurobehavioral disorders, downregulation of cortical and hippocampal expression of both BDNF/TrkB and cathepsin D, neural pathology, Aß accumulation, and altered microglial polarization caused by Aß. In vitro studies also confirmed that topical application of BDNF and/or AST reversed the Aß-induced cytotoxicity, apoptosis, mitochondrial distress, and synaptotoxicity and decreased expression of p-TrkB, p-Akt, p-GSK3ß, and ß-catenin in rat cortical neurons. The beneficial effects of combined ER (or BDNF) and AST therapy in vivo and in vitro were superior to ER (or BDNF) or AST alone. Furthermore, we observed that any gains from ER (or BDNF) and/or AST could be significantly eliminated by ANA-12, a potent BDNF/TrkB antagonist. These results indicate that whereas ER (or BDNF) and/or AST attenuate Aß pathology by reversing BDNF/TrkB signaling deficits and mitochondrial dysfunction, combining these two potentiates each other's therapeutic effects. In particular, AST can be an alternative therapy to replace ER.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catepsina D
/
Fator Neurotrófico Derivado do Encéfalo
Limite:
Animals
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Taiwan
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA