Circadian clock protein content and daily rhythm of locomotor activity are altered after chronic exposure to lead in rat
Front. Behav. Neurosci.. 2017-09-22; 11:
DOI: 10.3389/fnbeh.2017.00178
Lire sur PubMed
Sabbar M(1), Dkhissi-Benyahya O(2), Benazzouz A(3)(4), Lakhdar-Ghazal N(1).
Author information:
(1)Équipe de Recherche sur les Rythmes Biologiques, Neurosciences et
Environnement, Faculté des Sciences, Université Mohammed VRabat, Morocco.
(2)INSERM, Stem Cell and Brain Research Institute U1208, University of Lyon,
Université Claude Bernard Lyon 1Lyon, France.
(3)Institut des Maladies Neurodégénératives, Univ. de Bordeaux, UMR5293Bordeaux,
France.
(4)Centre National de la Recherche Scientifique, Institut des Maladies
Neurodégénératives, UMR5293Bordeaux, France.
Lead exposure has been reported to produce many clinical features, including
parkinsonism. However, its consequences on the circadian rhythms are still
unknown. Here we aimed to examine the circadian rhythms of locomotor activity
following lead intoxication and investigate the mechanisms by which lead may
induce alterations of circadian rhythms in rats. Male Wistar rats were injected
with lead or sodium acetate (10 mg/kg/day, i.p.) during 4 weeks. Both groups
were tested in the « open field » to quantify the exploratory activity and in the
rotarod to evaluate motor coordination. Then, animals were submitted to
continuous 24 h recordings of locomotor activity under 14/10 Light/dark (14/10
LD) cycle and in complete darkness (DD). At the end of experiments, the clock
proteins BMAL1, PER1-2, and CRY1-2 were assayed in the suprachiasmatic nucleus
(SCN) using immunohistochemistry. We showed that lead significantly reduced the
number of crossing in the open field, impaired motor coordination and altered
the daily locomotor activity rhythm. When the LD cycle was advanced by 6 h, both
groups adjusted their daily locomotor activity to the new LD cycle with high
onset variability in lead-intoxicated rats compared to controls. Lead also led
to a decrease in the number of immunoreactive cells (ir-) of BMAL1, PER1, and
PER2 without affecting the number of ir-CRY1 and ir-CRY2 cells in the SCN. Our
data provide strong evidence that lead intoxication disturbs the rhythm of
locomotor activity and alters clock proteins expression in the SCN. They
contribute to the understanding of the mechanism by which lead induce circadian
rhythms disturbances.