Elevated brain manganese induces motor disease by upregulating the kynurenine pathway of tryptophan metabolism.

ABSTRACT: Elevated brain levels of the essential metals manganese (Mn), copper, or iron induce motor disease. However, mechanisms of metal-induced motor disease are unclear and treatments are lacking. Elucidating the mechanisms of Mn-induced motor disease is particularly important because occupational and environmental Mn overexposure is a global public health problem. To address this, here we combined unbiased transcriptomics and metabolomics with functional studies in a mouse model of human environmental Mn exposure. Transcriptomics unexpectedly revealed that Mn exposure up-regulated expression of metabolic pathways in the brain and liver. Notably, genes in the kynurenine pathway of tryptophan metabolism, which produces neuroactive metabolites that impact neurological function, were up-regulated b

SUBMITTER: Warden AS 

PROVIDER: S-EPMC12036984 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature