Maternal Exposure to Nanoparticulate Titanium Dioxide Causes Inhibition of Hippocampal Development Involving Dysfunction of the Rho/NMDAR Signaling Pathway in Offspring.
J Biomed Nanotechnol
; 15(4): 839-847, 2019 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-30841976
ABSTRACT
Numerous studies have suggested that nano-TiO2 can be translocated to the brain via the placental barrier and blood brain barrier, leading to brain damage and cognitive impairment in both mice and rat offspring. The mechanism of nanoTiO2-induced neurotoxicity is still unclear, as is its role in the inhibition of hippocampal development. In this experiment, nano-TiO2 was employed to investigate whether the inhibition of the hippocampal development of mice offspring involved the alterations in the Rho signaling pathway following consecutive gavage of female mice between 7-21 days postpartum. The results showed that nano-TiO2 particles were concentrated in the hippocampus of offspring, resulting in reduced hippocampal indices and in inhibited axonal and dendritic growth. Furthermore, nano-TiO2 downregulated expression of N-methyl-D-aspartate receptor (NR)1, NR2A, NR2B, RhoGTPase, Ras-related C1 botulinum toxin substrate (Rac1), cell division cycle42 (Cdc42), phosphorylated cAMP response element binding protein (p-CREB), p21-activated kinase (PAK) 3, and PAK1, LIMK (LIM kinase) 1, p-LIMK1, activated Cdc42 kinase (ACK), and myotonic dystrophic kinaseassociated Cdc42-binding kinase (MRCK) and increased expression of RhoA, Rho kinase (ROCK) 1 and cyclin dependent kinase (Cdk) 5 in offspring. In addition, nano-TiO2 disrupted the balance of RhoA/Rac1, RhoA/Cdc42, and Rac1/Cdc42 ratios in the hippocampus of mice offspring. Taken together, these data imply that maternal exposure to nano-TiO2 inhibited development of hippocampal axons and dendrites of offspring may be correlated with the dysfunction of the Rho pathway and that N-methyl-D-aspartate receptors (NMDAR) may also mediate nano-TiO2-Rho pathway interactions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Exposição Materna
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
J Biomed Nanotechnol
Ano de publicação:
2019
Tipo de documento:
Article