Thorium-induced neurobehavioural and neurochemical alterations in Swiss mice

Abstract

Purpose: Thorium (²³²Th), a heavy metal radionuclide that targets the liver and skeleton, has been shown to accumulate in the central nervous system at low levels. The present study was aimed to investigate neurobehavioural and neurochemical changes in mice treated with ²³²Th at sub-lethal doses.

Materials and methods: Swiss albino mice were administered intraperitoneally with thorium nitrate. The chelation-based therapeutic effect of calcium diethylenetriamine pentaacetate (Ca-DTPA) was tested on the ²³²Th-treated mice. ²³²Th localisation was determined in brain regions by the Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method. Achetylcholine esterase (AChE) activity in different brain regions was evaluated to assess the cholinergic function of mice CNS. Oxidative damage was evaluated by assessing the activities of antioxidant enzymes (i.e., superoxide dismutase and catalase) and the level of lipid peroxidation. The neurobehavioural alteration in the treated mice was studied by the shuttle box method.

Results: ²³²Th accumulation found in different brain regions followed the order: Cerebellum (Cbl) > cortex (Ctx) > hippocampus (Hp) > striatum (Str). However, removal of ²³²Th by Ca-DTPA was significant from brain regions like Cbl, Ctx and Str but not from Hp. A significant increase in lipid peroxidation and acetylcholine esterase (AChE) activity was observed in the treated mice but activities of superoxide dismutase and catalase was found substantially decreased. ²³²Th treatment impaired the learning and memory-based neurobehaviour of the mice. Furthermore, our data suggest that Ca-DTPA injection in ²³²Th-treated animals failed to improve the neurobehaviour of the treated mice, perhaps because Ca-DTPA could not decorporate ²³²Th or mitigate ²³²Th-mediated neurochemical changes effectively from/in hippocampus, a brain region implicated in learning and memory response.

Conclusion: Administration of ²³²Th in mice caused neurobehavioural alteration and impairment of cholinergic function, which might be the consequence(s) of oxidative stress induction in different brain regions.

Key words:

• Behavioural effect
• natural thorium
• acetylcholine esterase
• antioxidant enzymes
• oxidative stress
• neurotoxicity