Effects of prenatal exposure to THC on hippocampal neural development in offspring.
Toxicol Lett
; 374: 48-56, 2023 Feb 01.
Article
de En
| MEDLINE
| ID: mdl-36529297
Cannabis use is a worldwide issue with the development of legalization. Prenatal exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, is related to affect fetal nervous system development. In our present study, we administered THC to pregnant mice from gestational day 5.5-12.5. Differences in neuronal cell composition and organization between the two groups were found by staining sections of the offspring hippocampus at PND21. In addition, RNA-seq of hippocampal tissue also suggested differences in gene expression due to THC treatment, especially significant enrichment to neurogenesis and neural differentiation. Subsequently, the effect of THC treatment on the proliferation and differentiation capacity of neural stem cells (NSCs) was confirmed. Based on the RNA-seq results, we selected the differentially expressed transcription factor MEF2C for validation. The effect of THC treatment on NSCs differentiation was found to be regulated by knocking down the expression of MEF2C in NSCs. Considering that THC is an agonist of cannabinoid receptor (CB1R), the differentiation outcome of NSC after THC treatment was significantly rescued, by pretreating with the CB1R inhibitor Rimonabant. Notably, pretreatment with Rimonabant restored the expression of MEF2C. Taken together, the present results suggested that THC regulated the MEF2C pathway through CB1R and had an impact on hippocampal neurodevelopment.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Effets différés de l'exposition prénatale à des facteurs de risque
/
Hallucinogènes
Limites:
Animals
/
Pregnancy
Langue:
En
Journal:
Toxicol Lett
Année:
2023
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Pays-Bas