ER stress mediatedautophagy contributes to neurological dysfunction in traumatic brain injury via the ATF6 UPR signaling pathway.
Mol Med Rep
; 23(4)2021 04.
Article
em En
| MEDLINE
| ID: mdl-33537827
ABSTRACT
A major public health problem, traumatic brain injury (TBI) can cause severe neurological impairment. Although autophagy is closely associated with the pathogenesis of TBI, the role of autophagy in neurological deficits is unclear. The purpose of the present study was to investigate the molecular mechanisms of endoplasmic reticulum (ER) stressinduced autophagy and its detrimental effects on neurological outcomes following TBI. A rat model of TBI was established by controlled cortical impact. ER stress activation, autophagy induction and autophagic flux dysfunction were examined in the damaged hippocampus postTBI. Pharmacological inhibition of ER stress significantly blocked posttraumatic autophagy activation, as evidenced by decreased conversion of microtubuleassociated protein 1 light chain 3 (LC3)I to LC3II and Beclin1 expression levels in the hippocampus region. Short hairpin RNAmediated activating transcription factor 6 knockdown significantly prevented ER stressmediated autophagy stimulation via targeting essential autophagic genes, including autophagy related (ATG)3, ATG9 and ATG12. Furthermore, neurological scores, foot fault test and Morris water maze were used to evaluate the neurological functions of TBI rats. The results revealed that the blockage of ER stress or autophagy attenuated TBIinduced traumatic damage and functional outcomes. In conclusion, these findings provided new insights into the molecular mechanisms of ER stressinduced autophagy and demonstrated its potential role in neurological deficiency following TBI.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Transdução de Sinais
/
Fator 6 Ativador da Transcrição
/
Estresse do Retículo Endoplasmático
/
Lesões Encefálicas Traumáticas
/
Doenças do Sistema Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article