Disruption of cellular Calcium homeostasis and mitochondrial function following chronic methylmercury treatment.

摘要

Methylmercury (MeHg) is a potent environmental neurotoxicant that impairs several neurological functions upon short and long-term exposure. MeHg causes cell-type specific damage in the cerebellum and this effect seems to be due to a disruption of intracellular calcium ([Ca2+]i) homeostasis and voltage-gated Ca2+ channel (VGCC) function. The striatum may be a sensitive target due to its high expression of Cav1.3, an L-type VGCC. Exposure to low levels of MeHg throughout ones lifetime is of contemporary concern. In viro and in vivo studies were designed to mimic a lifetime exposure to low-levels of MeHg. Following prolonged exposure to low-nanomolar MeHg in vitro we found that MeHg causes a time- and subtype-dependent block of VGCCs, as well as increased resting [Ca2+]i. Chronic MeHg exposure in vivo suggests that MeHg interacts with AMPA receptors altering the post-synaptic response to glutamate at striatal medium spiny neurons. Chronic MeHg treatment also altered striatal synaptosomal mitochondrial function. This work contributes to our understanding of the consequences of long-term exposure to MeHg on neuronal function.