Neurotoxicity and Brain Regional Distribution of Manganese in Mice

Abstract

Manganese (Mn) is known to cause neurotoxicity in the central nervous system similar to Parkinsonism in man, but the mechanism underlying remains to be well clarified. Catalepsy is used to observe Parkinsonism in laboratory animals. In the present study, effects of repeated injection of Mn chloride (MnCl₂) on catalepsy, dopamine receptors and distribution of ⁵⁴Mn in the brain were investigated. [Methods] Female ICR mice were injected with 0, 10, 30 or 50 mg/kg/day of MnCl₂ for 3 days, and examined for catalepsy and the binding ability of striatum, hippocampus and cerebral cortex to [³H]haloperidol to detect and change of dopamine D₂‐receptors. Whole‐body burden and disposition of ⁵⁴Mn in the brain regions and liver were determined after the repeated injection of ⁵⁴MnCl₂. Mice were given l‐dopa at 25 mg/kg 2 hr prior to MnCl₂ injection to examined if the catalepsy was abolished. [Results] Mice showed catalepsy following injection of MnCl₂ at 50 mg/kg, but not with less than 30 mg/kg. The catalepsy initiated about 60, 60 and 30 min after injection of MnCl₂ on the 1st, 2nd and 3rd day, respectively, and lasted for about 60 min. l‐dopa slightly reversed the catalepsy. The binding of [³H]haloperidol in the three brain regions from mice treated with MnCl₂ was lower than that from control. The concentration of ⁵⁴Mn in the striatum and remaining areas, including substantia nigra, was the highest in the brain regions examined. [Conclusion] Since l‐dopa slightly alleviated catalepsy by MnCl₂, and binding of [³H]haloperidol was decreased in brain regions, MnCl₂ might induce catalepsy by suppressing D₂ receptors in the striatum‐substantia nigra.