Consequences of manganese intoxication on the circadian rest-activity rhythms in the rat.
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 (10mg/kg, i.p) for 5weeks. Locomotor activity was assessed under a light-dark (LD) cycle, constant darkness (DD) and during adjustment to 6h 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±0.07h in Mn group vs. 24.01±0.04h 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.
University Mohamed V, Faculty of Sciences, Unit of Research on Biological Rhythms and Environment, Rabat, Morocco.
Safa
S
Bouabid
Laboratory of Neurophysiology, Molecular Cell Biology Department, Leiden University Medical Center, PO Box 9600 Mailbox S5-P, 2300 RC Leiden, The Netherlands.
Karim
K
Fifel
Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
Abdelhamid
A
Benazzouz
University Mohamed V, Faculty of Sciences, Unit of Research on Biological Rhythms and Environment, Rabat, Morocco. Electronic address: nlakhdarghazal@gmail.com.
Nouria
N
Lakhdar-Ghazal
D056044:Actigraphy; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D008297:Male; D008345:Manganese / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D017440:Photoperiod; D011897:Random Allocation; D017208:Rats, Wistar; D013997:Time Factors
D008345:Manganese
Parkinsonism; circadian rhythm; entrainment; light–dark cycles; manganese; rest-activity