<p>Long-term exposure to excess manganese can lead to a condition known as manganism, which is characterized by irreversible neuropsychiatric and extrapyramidal dysfunction resembling Parkinson’s disease. Excessive exposure to manganese not only increases manganese levels in the body, but can also disrupt the homeostasis of other trace elements. Elemental imbalance has been reported as a risk factor for several neurodegenerative diseases, and restoring elemental homeostasis may be a potential strategy to combat these conditions. We investigated the relationship between trace element dysregulation and cognitive function following different doses of manganese exposure in multiple tissues. Our results indicated that manganese exposure resulted in decreased learning and memory abilities, as well as impaired balance in rats. Manganese imbalance disrupted elemental homeostasis in several tissues. Hippocampal elemental dysregulation was associated with cognitive performance, and changes in aluminum levels in tissues also appeared to be closely related to cognitive function. Curcumin intervention ameliorated manganese-induced behavioural abnormalities and partially reversed manganese-induced elemental dysregulation, demonstrating its potential as a regulator of elemental homeostasis.</p>