Chronic exposure to aluminum reduces tyrosine hydroxylase expression in the substantia nigra and locomotor performance in rats.

Aluminum (Al) is a neurotoxic agent that accumulates in the substantia nigra of patients affected by Parkinson's disease and in other cerebral areas of different neurodegenerative pathologies. Al has been associated with neuronal and glial dysfunctions, and neuronal changes have been suggested to affect several neurotransmitter systems including the dopaminergic system. The present study was designed to evaluate by means of immunohistochemistry using antibodies against tyrosine hydroxylase (TH; the rate-limiting enzyme of dopamine synthesis) the effects of chronic Al exposure (0, 3%) in drinking water during 4 months in adulthood or since intra-uterine age in the substantia nigra. Our results show a significant decrease in the number of cells labeled by the antibody against TH in rats treated with Al compared to controls. The TH-immunoreactive decrease following Al treatment is accentuated in the rat group treated since intrauterine age. In both treated groups, Al exposure induced a significant decrease of locomotor performance. Interestingly, as for TH-immunoreactivity, the decreased locomotor activity was also accentuated in the group treated since intrauterine age. The Al-induced TH alterations may be one of the causes of aluminum-induced neurotoxicity.