Role of p75 neurotrophin receptor in neuronal autophagy in intracerebral hemorrhage in rats through the mTOR signaling pathway.
Cell Cycle
; 19(3): 376-389, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31924125
Rupture of weakened blood vessels could lead to severe intracerebral hemorrhage (ICH) and brain injuries. This study was designed to explore the roles of p75 neurotrophin receptor (p75NTR) in neuronal autophagy in ICH rats. An ICH rat model was established, and then gain and loss of functions of p75NTR in rat tissues were performed. Then, the pathologic morphology, water content, and inflammation in brain tissues were assessed. Western blot analysis was applied to detect the levels of inflammatory proteins, apoptosis- and autophagy-related proteins, and the mammalian target of rapamycin (mTOR) pathway-related proteins. Neuronal autophagy was further measured with mTOR activated. In vitro experiments were also performed on brain microvascular endothelial cells (BMECs) and astrocytes. Consequently, we found p75NTR knockdown improved the pathologic morphology with reduced neuron damage, water content, permeability of blood-brain barrier and inflammation in ICH rat brain tissues. Besides, Knockdown of p75NTR decreased neuronal apoptosis and inactivated mTOR signaling pathway, but it elevated the levels of autophagy-related proteins. In vivo results were reproduced in in vitro experiments. This study demonstrated that knockdown of p75NTR could promote neuronal autophagy and reduce neuronal apoptosis via inactivating the mTOR pathway. We hope these findings could provide new therapeutic options for ICH treatment.
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Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Hemorragia Cerebral
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Receptores de Fatores de Crescimento
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Serina-Treonina Quinases TOR
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Proteínas do Tecido Nervoso
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Neurônios
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article