Developmental exposure to mercury chloride impairs social behavior in male offspring dependent on genetic background and maternal autoimmune environment

Abstract

To date, the connection between inorganic mercury (Hg) and social behavior remains incompletely understood. The aim of this study was to investigate the influence of maternal autoimmunity by inorganic Hg (Hg²⁺) exposure on social behavior of offspring. Wild-type (WT) and immunoglobulin deficient (Ig^-/-) B10.S dams fertilized by male WT B10.S or SJL mice were treated with 50 μM Hg chloride (HgCl₂). Non-pregnant female WT B10.S mice were used to investigate factors regulating HgCl₂-induced autoimmunity to brain. HgCl₂ selectively impaired social behavior in male offspring, but not female offspring from WT B10.S dams × male SJL, in that only male offspring displayed reduced time distribution with the stranger mouse, decreased sniffing to the stranger mouse and increased self-grooming. HgCl₂ did not disrupt social behavior of male or female offspring from WT B10.S dams × male WT B10.S or Ig^-/- B10.S dams × male SJL. The offspring from WT and Ig^-/- B10.S dams × male SJL had equivalent autoimmunity to brain antigens during HgCl₂ exposure, indicating that maternal, but not offspring-derived anti-brain antibodies (Ab) impaired social behavior of the offspring. Non-pregnant WT B10.S mice treated with HgCl₂ had increased anti-brain Ab dependent on increase in CD4 T cell activation and IFNγ signaling to macrophages. IFNγ interaction with macrophages drove B cells and plasma cells to produce IgG. Therefore, HgCl₂ selectively impaired social behavior in males with certain genetic background via maternally derived anti-brain Ab production, thus providing a novel insight into our current understanding of Hg toxicity.

Keywords: Anti-brain antibody; Autoimmune; IFNγ; Macrophage; Mercury chloride; Social behavior.