DHF-7 Ameliorates Behavioral Disorders and White Matter Lesions by Regulating BDNF and Fyn in a Mouse Model of Schizophrenia Induced by Cuprizone and MK-801.
Int J Neuropsychopharmacol
; 25(7): 600-612, 2022 08 04.
Article
em En
| MEDLINE
| ID: mdl-35353146
ABSTRACT
BACKGROUND:
Schizophrenia is a psychiatric disorder including multiple clinical symptoms such as severe psychosis and cognitive dysfunction. DHF-7 is a novel dihydroflavanone derivative that was designed and synthesized to treat schizophrenia. This study aimed to investigate the effects and mechanisms of DHF-7 in a mouse model of schizophrenia induced by a combination of cuprizone and MK-801.METHODS:
After intragastric administration of DHF-7 for 7 weeks, open field, Y-maze, and novel object recognition tests were performed to detect behavioral changes in the mouse model. White matter lesions and myelin loss were determined using transmission electron microscopy and oil red O staining. Western blotting and immunohistochemistry were used to detect the expression of the related proteins.RESULTS:
The results showed that DHF-7 treatment significantly improved cognitive impairment and positive symptoms in the model mice. Moreover, DHF-7 alleviated white matter lesions and demyelination and promoted the differentiation and maturation of oligodendrocytes for remyelination in the corpus callosum of model mice. The mechanistic study showed that DHF-7 increased the expression of brain-derived neurotrophic factor and phosphorylated Fyn, thus activating the tyrosine kinase receptor B (Trk B)/Fyn/N-methyl-D-aspartate receptor subunit 2 B (NMDAR2B) and Raf/mitogen-activated protein kinase (MEK)/ extracellular signal-related kinase (ERK) signaling pathways.CONCLUSIONS:
Our results provide an experimental basis for the development of DHF-7 as a novel therapeutic agent for schizophrenia.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Fator Neurotrófico Derivado do Encéfalo
/
Proteínas Proto-Oncogênicas c-fyn
/
Substância Branca
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Neuropsychopharmacol
Assunto da revista:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China