Induction of autoimmunity to brain antigens by developmental mercury exposure

A.SW mice, which are known to be prone to mercury (Hg)-induced immune nephritis, were assessed for their ability to develop autoimmunity to brain antigens after developmental exposure to Hg. Maternal drinking water containing subclinical doses of 1.25μM methyl Hg (MeHg) or 50μM Hg chloride (HgCl(2)) were used to evaluate developmental (exposure from gestational day 8 to postnatal day 21) induction of immune responses to brain antigens. Only HgCl(2) induced autoantibody production; the HgCl(2)-exposed offspring showed an increased number of CD4(+) splenic T cells expressing CD25 and V(β) 8.3 chains, and the brain-reactive immunoglobulin G (IgG) antibodies were predominantly against nuclear proteins (30 and 34 kD). The antibodies were deposited in all brain regions. Although male and female A.SW mice exposed to HgCl(2) showed deposition of IgG in multiple brain regions, inflammation responses were observed only in the cerebellum (CB) of female A.SW mice; these responses were associated with increased levels of exploratory behavior. The developmental exposure to MeHg also induced inflammation in the CB and increased exploratory behavior of the female A.SW mice, but the change did not correlate with increased IgG in the brain. Interestingly, the non-Hg-exposed female A.SW mice habituated (adapted to the information and/or stimuli of a new environment) more than the male A.SW mice during exploratory behavior assessment, and the Hg exposure eliminated the habituation (i.e., no changes in behavior with subsequent trials), making the female behaviors more like those of the male A.SW mice. Additionally, gender differences in A.SW brain cytokine expressions prior to Hg exposure were eliminated by the Hg exposure.