Chronic inorganic mercury exposure induces sex-specific changes in central TNFα expression: importance in autism?

Abstract

Mercury is neurotoxic and increasing evidence suggests that environmental exposure to mercury may contribute to neuropathologies including Alzheimer's disease and autism spectrum disorders. Mercury is known to disrupt immunocompetence in the periphery, however, little is known about the effects of mercury on neuroimmune signaling. Mercury-induced effects on central immune function are potentially very important given that mercury exposure and neuroinflammation both are implicated in certain neuropathologies (i.e., autism). Furthermore, mounting evidence points to the involvement of glial activation in autism. Therefore, we utilized an in vivo model to assess the effects of mercury exposure on neuroimmune signaling. In prairie voles, 10 week mercury exposure (60ppm HgCl(2) in drinking water) resulted in a male-specific increase in TNFα protein expression in the cerebellum and hippocampus. These findings are consistent with our previously reported male-specific mercury-induced deficits in social behavior and further support a role for heavy metals exposure in neuropathologies such as autism. Subsequent studies should further evaluate the mechanism of action and biological consequences of heavy metals exposure. Additionally, these observations highlight the potential of neuroimmune markers in male voles as biomarkers of environmental mercury toxicity.

Fig. 1

TNFα expression in male vole brain was elevated in both the hippocampus and cerebellum 6 h after peripheral administration of 3 mg/kg LPS. * P < 0.05 vs. 0 hr.

Fig 2

Neuroimmune factor responses in vole brain after chronic mercury exposure. Ten weeks of chronic exposure to mercury in drinking water altered TNFα expression in a sex-specific fashion in the cerebellum and hippocampus of prairie voles (A, B). In both brain regions, exposure to mercury increased TNFα in male voles but not in females. This mercury exposure paradigm did not alter the expression of CCL2 (C, D) or CXCL10 (E, F). * - significantly greater than water-treated voles of either sex. # - significantly different from within-treatment opposite sex animals.