Propionic acid induces dendritic spine loss by MAPK/ERK signaling and dysregulation of autophagic flux.
Mol Brain
; 13(1): 86, 2020 06 02.
Article
em En
| MEDLINE
| ID: mdl-32487196
ABSTRACT
Propionic acid (PPA) is a short-chain fatty acid that is an important mediator of cellular metabolism. It is also a by-product of human gut enterobacteria and a common food preservative. A recent study found that rats administered with PPA showed autistic-like behaviors like restricted interest, impaired social behavior, and impaired reversal in a T-maze task. This study aimed to identify a link between PPA and autism phenotypes facilitated by signaling mechanisms in hippocampal neurons. Findings indicated autism-like pathogenesis associated with reduced dendritic spines in PPA-treated hippocampal neurons. To uncover the mechanisms underlying this loss, we evaluated autophagic flux, a functional readout of autophagy, using relevant biomedical markers. Results indicated that autophagic flux is impaired in PPA-treated hippocampal neurons. At a molecular level, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway was activated and autophagic activity was impaired. We also observed that a MAPK inhibitor rescued dendritic spine loss in PPA-treated hippocampal neurons. Taken together, these results suggest a previously unknown link between PPA and autophagy in spine formation regulation in hippocampal neurons via MAPK/ERK signaling. Our results indicate that MAPK/ERK signaling participates in autism pathogenesis by autophagy disruption affecting dendritic spine density. This study may help to elucidate other mechanisms underlying autism and provide a potential strategy for treating ASD-associated pathology.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Propionatos
/
Autofagia
/
Sistema de Sinalização das MAP Quinases
/
Espinhas Dendríticas
/
MAP Quinases Reguladas por Sinal Extracelular
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article