Cyclosporin A impairs neurogenesis and cognitive abilities in brain development via the IFN-γ-Shh-BDNF pathway.
Int Immunopharmacol
; 96: 107744, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33993101
ABSTRACT
A wealth of evidence indicate that the peripheral immune activation alters brain development. However, it is still largely unclear whether and how peripheral immunosuppression affects neurodevelopment. Here, we found that the immunosuppressant cyclosporin A (CsA) decreased the number of BrdU+, BrdU+/DCX+, BrdU+/NeuN + cells in the hippocampus, impaired learning and memory and inhibited protein levels of the shh signaling pathway, including Shh, Smo and Gli1. However, the shh pathway receptor agonist SAG could block the impairment of cognitive ability and the decrease of hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) level induced by CsA. We also found that CsA decreased the level of interferon-gamma (IFN-γ), while up-regulation of IFN-γ altered the inhibitory effect of the shh signaling pathway and the decrease of BDNF induced by CsA. Collectively, these data indicate that peripheral CsA impairs neurogenesis and cognition in brain development through downregulating the IFN-γ-Shh-BDNF pathway. The present study guides us to correctly apply immunomodulatory drugs in early life and suggests that the IFN-γ-Shh-BDNF pathway may represent a novel protective target for neurodevelopment under the condition of immunosuppression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interferon gama
/
Ciclosporina
/
Transtornos Cognitivos
/
Fator Neurotrófico Derivado do Encéfalo
/
Proteínas Hedgehog
/
Hipocampo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article