Consequences of manganese intoxication on the circadian rest-activity rhythms in the rat

• Manganese induced alterations of the circadian pattern of rest-activity rhythm.
• Manganese treatment induced a more fragmented and less stable rest-activity rhythm.
• Manganese reduces the total amount of 24-h locomotor activity and the nocturnal activity.
• These deficits led to a significant decrease in the amplitude of the rest-activity rhythm.
• A 6-h advanced activity revealed abnormal entrainment to the new photoperiod after manganese.

Manganese (Mn) intoxication is associated with neurological dysfunctions collectively known as Parkinsonism or Manganism. Like in Parkinson’s disease, Manganism is associated with motor disturbances, together with non-motor symptoms including cognitive and neuropsychiatric deficits. Although sleep dysfunctions are commonly reported among workers exposed to Mn, their underlying pathophysiology remains unknown. In this study, we investigated the rest-activity rhythms in rats treated daily with MnCl2 (10 mg/kg, i.p) for 5 weeks. Locomotor activity was assessed under a light–dark (LD) cycle, constant darkness (DD) and during adjustment to 6 h shifts of the LD cycle. In LD conditions, Mn-treated rats exhibited a more fragmented and less stable rest-activity rhythm in addition to a reduction in the total 24-h amount of locomotor activity as well as in the activity confined to the active dark phase of the LD. Consequently, a significant decrease in the amplitude of the rest-activity rhythm was observed. These disturbances were displayed during and after Mn treatment. Furthermore, after the 6-h phase advance of the LD cycle, Mn-treated rats failed to re-adjust accurately their behavioral activity to the new shifted LD cycle. Upon release from LD into DD, Mn-treated rats expressed a normal and stable free-running period of their rest-activity rhythm (23.92 ± 0.07 h in Mn group vs. 24.01 ± 0.04 h in control rats). However, their rest-activity rhythm remained highly fragmented and less stable. Our results provide the first evidence that chronic Mn intoxication leads to impairment of rest-activity rhythms in addition to the motor and non-motor disturbances reported in Manganism.