Exposure to lead on expression levels of brain immunoglobulins, inflammatory cytokines, and brain-derived neurotropic factor in fetal and postnatal mice with autism-like characteristics

ABSTRACT

Autism spectrum disorders (ASD) are neurodevelopmental disorders, and their incidence is increasing worldwide. Increased exposure to environmental metal lead (Pb) has been proposed as a risk factor associated with ASD. In the present study, BTBR T+ tf/J (BTBR) mice with ASD-like behavioral characteristics and control FVB mice were exposed gestationally and/or neonatally to Pb, and compared with highly social FVB mice to investigate neuroimmunological abnormalities. IgG1 and IgG2a levels in fetal brains from BTBR dams exposed to Pb (BTBR-Pb) were significantly higher than those of BTBR-controls (BTBR-C). However, this change did not occur in FVB mice exposed to Pb. The IgG1:IgG2a ratio was higher in both fetal and postnatal brains of BTBR mice compared to FVB animals regardless of Pb exposure. The IL-4:IFN-γ ratio was elevated in BTBR-Pb relative to BTBR-C mice, but this ratio was not markedly affected following Pb exposure in FVB animals. These findings suggest the potential for a Pb-driven predominant T_H2-like reactivity profile in brain microenvironment present in BTBR mice. Brain-derived neurotrophic factor was decreased in fetal and postnatal BTBR-Pb brains relative to BTBR-C brains but not in FVB-Pb relative to FVB-C mice. Taken together, data demonstrate that Pb exposure might contribute to developmental brain abnormalities associated with ASD, particularly in individuals with genetic susceptibility to ASD.

KEYWORDS:

• autism spectrum disorders
• fetal mice
• postnatal mice
• metal lead
• brain immunotoxicity

Disclosure Statement

The authors declare no conflicts of interest in association with the present study.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was supported by a grant from the National Research Foundation of Korea (grant no. 2010-0022169), and the educational training program for the management of information on the hazards and risks of chemical substances funded by the Ministry of Environment of Korea (entrusted to the Korea Chemicals Management Association);Ministry of Environment of Korea Educational program for chemical hazards and risk;