Contributions of Retinoid Signaling to Autism-like Behaviors Induced by Early Postnatal Lead Exposure in the Mouse Cerebellum

TL;DR

Early lead exposure in mice leads to autism-like behaviors, possibly through disruption of retinoid signaling in the cerebellum.

Contribution

This study identifies retinoid signaling as a potential mechanism linking early lead exposure to autism-like behaviors in mice.

Findings

Pb-exposed offspring showed social deficits, repetitive behaviors, and cognitive impairments.

Cerebellar Pb levels were elevated, and Purkinje cells were reduced in number.

Proteomic analysis revealed 45 differentially expressed proteins, with retinoid signaling disrupted.

Abstract

Autism spectrum disorder (ASD) is a group of neurodevelopmental dysfunctions characterized by a heterogeneous etiology that involves gene–environment interactions. Early postnatal lead (Pb) exposure has been found to be associated with the etiology of ASD, but the mechanisms remain unclear. The present study aims to investigate the effects of early Pb exposure on the emergence of ASD-like behaviors in offspring and to evaluate its potential relationship with morphological changes and underlying mechanisms in the cerebellum. The study established a mouse model to study early postnatal Pb exposure and examined ASD-like behaviors through the open field test, novel object recognition test, marble burying test, and three-chamber social test. Quantification of Pb levels was performed in cerebellar tissue, examination of Purkinje cell morphology was carried out, and identification of differential protein expression was conducted using TMT-based quantitative proteomics. The study revealed that the offspring of Pb-exposed mice showed significant social deficits, increased repetitive behaviors, and cognitive impairments. The cerebellum showed both elevated Pb levels and a reduction in Purkinje cells. Proteomic analysis identified 45 proteins that were differentially expressed, showing disruption in the retinoid signaling pathway. These findings demonstrate that early postnatal Pb exposure leads to ASD traits and that retinoid signaling may be a key pathway in the cerebellum, at least in part.

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