The precise mechanism of methylmercury-induced neuronal disorders is unclear. Our research group previously found that methylmercury treatment altered the expression levels of genes in the murine cerebellum, upregulating the expression of 21 genes and downregulating that of 11 genes [
24]. Increased expression was observed for several genes encoding the chemokines Ccl2, Ccl4, Ccl7, Ccl9, and Ccl12. Chemokines have been hypothesized to be involved in physiological synaptic signal transmission and developmental processes in the central nervous system [
25], and their roles in methylmercury toxicity should therefore be investigated. We found that in the murine cerebrum, mRNA levels of these five chemokines increased significantly in response to methylmercury, and a similar response was observed in the kidney, with the exception of
Ccl4 expression. No significant effect on chemokines was observed in the liver and spleen [
26]. Our study of changes in chemokine gene expression in the murine cerebellum, cerebrum, kidney, liver, and spleen found that methylmercury-induced upregulation of
Ccl3 and
Ccl4 expression [
27], implying a specificity in methylmercury toxicity to the central nervous system. We also found that methylmercury increased
Ccl2 expression in human 1321 N1 astrocytes and elevated nuclear levels of the NF-κB p65 subunit; overexpression of
CCL2 was inhibited by suppressing p65 expression using RNA interference [
28]. More recently, we examined the transcriptional regulatory mechanism that induces
Ccl4 expression in C17.2 mouse neural stem cells, and found that methylmercury stimulated the region upstream of the transcription start site and increased nuclear levels of serum response factor (SRF) and the amount bound to the
Ccl4 gene promoter [
29]. We also confirmed that methylmercury activated p38 and ERK, which are a part of the mitogen-activated protein kinase pathway, and these activations were involved in the induction of
Ccl4 expression [
29].