Perinatal manganese exposure: behavioral, neurochemical, and histopathological effects in the rat.

Manganese chloride (Mn) was dissolved in the drinking water (0, 2, or 10 mg/ml) of dams and their litters from conception until postnatal day (PND) 30. Parturition was uneventful in the Mn-exposed rats and no physical abnormalities were observed. The rats exposed to 10 mg/ml Mn showed a 2.5-fold increase in cortical Mn levels. Their weight gain was attenuated from PND 9-24 and they were hyperactive at PND 17. Neither the 2 nor the 10 mg/ml Mn-exposed groups differed from the controls on the elevated plus apparatus or on the Morris water maze and the radial arm maze. Brain monoamine levels and choline acetyltransferase activity were affected. Tyrosine hydroxylase immunohistochemistry showed that dopamine cells of the substantia nigra were intact. Glial fibrillary acidic protein immunoreactivity was not increased in cortex, caudate, and hippocampus. However, both the low- and high-dose Mn-exposed groups showing thinning of the cerebral cortex. This could have resulted from perinatal malnutrition or from a direct effect of Mn on cortical development.