Acute enhancement of non-rapid eye movement sleep in rats after drinking water contaminated with cadmium chloride.
Cadmium (Cd) is a heavy metal widely used or effused by industries. Serious environmental Cd pollution has been reported over the past two centuries, whereas the mechanisms underlying Cd-mediated diseases are not fully understood. Interestingly, an increase in reactive oxygen species (ROS) after Cd exposure has been shown. Our group has demonstrated that sleep is triggered via accumulation of ROS during neuronal activities, and we thus hypothesize the involvement of Cd poisoning in sleep-wake irregularities. In the present study, we analyzed the effects of Cd intake (1-100 ppm CdCl₂ in drinking water) on rats by monitoring sleep encephalograms and locomotor activities. The results demonstrated that 100 ppm CdCl₂ administration for 28 h was sufficient to increase non-rapid-eye-movement (non-REM) sleep and reduce locomotor activities during the night (the rat active phase). In contrast, free-running locomotor rhythms under constant dim red light and their re-entrainment to 12:12-h light/dark cycles were intact under chronic (1 month) 100 ppm CdCl₂ administrations, suggesting a limited influence on circadian clock movements at this dosage. The relative amount of oxidized glutathione increased in the brain after the 28-h 100 ppm CdCl₂ administrations similar to the levels in cultured astrocytes receiving H₂O₂ or CdCl₂ in culture medium. Therefore, we propose Cd-induced sleep as a consequence of oxidative stress. As oxidized glutathione is an endogenous sleep substance, we suggest that Cd rapidly induces sleepiness and influences activity performance by occupying intrinsic sleep-inducing mechanisms. In conclusion, we propose increased non-REM sleep during the active phase as an index of acute Cd exposure.
Graduate School of Science and Engineering, University of Toyama, 3190, Gofuku, Toyama, 930-8555, Japan.
Katsuya
K
Unno
Kurumi
K
Yamoto
Kouhei
K
Takeuchi
Aya
A
Kataoka
Tomoya
T
Ozaki
Takatoshi
T
Mochizuki
Kazuki
K
Honda
Nobuhiko
N
Miura
Masayuki
M
Ikeda
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D019256:Cadmium Chloride / Q000008:administration & dosage* / Q000009:adverse effects*; D002940:Circadian Rhythm / Q000187:drug effects; D060766:Drinking Water / Q000737:chemistry*; D017781:Genes, Immediate-Early / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012894:Sleep Stages / Q000187:drug effects*
D060766:Drinking Water; D017382:Reactive Oxygen Species; D005978:Glutathione; D019256:Cadmium Chloride; D019803:Glutathione Disulfide
cadmium; circadian rhythms; electroencephalogram; oxidized glutathione; rats; slow wave sleep