Melatonin suppresses inflammation and bloodâbrain barrier disruption in rats with vascular dementia possibly by activating the SIRT1/PGC-1α/PPARγ signaling pathway.
Inflammopharmacology
; 31(3): 1481-1493, 2023 Jun.
Article
en En
| MEDLINE
| ID: mdl-37017851
ABSTRACT
Chronic cerebral hypoxia (CCH) is caused by a reduction in cerebral blood flow, and cognitive impairment has been the predominant feature that occurs after CCH. Recent reports have revealed that melatonin is proficient in neurodegenerative diseases. However, the molecular mechanism by which melatonin affects CCH remains uncertain. In this study, we aimed to explore the role and underlying mechanism of melatonin in inflammation and bloodâbrain barrier conditions in rats with CCH. Male Wistar rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) to establish the VAD model. Rats were randomly divided into four groups Sham, BCCAO, BCCAO treated with melatonin (10 mg/kg), and BCCAO treated with resveratrol (20 mg/kg). All drugs were administered once daily for 4 weeks. Our results showed that melatonin attenuated cognitive impairment, as demonstrated by the Morris water maze tests. Furthermore, melatonin reduced the activation of inflammation by attenuating the phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha (pIκBα), causing the suppression of proteins related to inflammation and inflammasome formation. Moreover, immunohistochemistry revealed that melatonin reduced glial cell activation and proliferation, which were accompanied by Western blotting results. Additionally, melatonin also promoted the expression of sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), and peroxisome proliferator-activated receptor-gamma (PPARγ), causing attenuated bloodâbrain barrier (BBB) disruption by increasing tight junction proteins. Taken together, our results prove that melatonin treatment modulated inflammation and BBB disruption and improved cognitive function in VaD rats, partly by activating the SIRT1/PGC-1α/PPARγ signaling pathway.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Demencia Vascular
/
Melatonina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2023
Tipo del documento:
Article