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Latest Paper:
Life Sci. 2003 Jun 6;73 (3):327-35
12757840
Cit:7
C Martin,
H Dutertre-Catella,
M Radionoff,
M Debray,
C Benstaali,
P Rat,
M Thevenin,
Y Touitou,
J-M Warnet
Laboratoire de Toxicologie, Faculté de Pharmacie, Université Paris V, 4 Avenue de l'Observatoire, 75006 Paris, France.
It has been shown that some cytochrome P450-dependent enzyme activities could present daily fluctuations, particularly CYP3A isoenzymes which are enhanced during the dark period. The aim of this study was to investigate whether age and photoperiodic conditions at different circadian stages could influence these fluctuations. Young mature (10 weeks) and old (22 months) Wistar rats were initially exposed to light-dark cycles 12:12 during 4 weeks, and secondly 18:6 for either one week or six weeks. Erythromycin N-demethylase (CYP3A-dependent), 7-ethoxycoumarin O-deethylase (CYP1A-dependent) and aniline 4-hydroxylase (CYP2E-dependent) activities were determined in liver and kidney microsomes at different hours after darkness onset (HADO). In addition, liver and kidney GSH, GSHPx, ATP, TBARS were determined. During the LD 12:12 cycle, while no significant modification was observed in CYP1A- and 2E-dependent enzyme activities as functions of HADO, erythromycin N-demethylase activity (CYP3A-dependent) showed a significant increase during the second third of the dark period in both young and old rats. After switching to a LD 18:6 cycle, this variation was still observed during second third of the dark period, to a lesser but still significant degree, with no difference between one week and six weeks exposure to the new photoperiod. It can be noted that the old rats showed a significantly lower level of erythromycin N-demethylase activity than the young rats, in parallel to a decrease in GSH, GSHPx and ATP, and an increase in TBARS.These results confirm the lower resistance of old animals to oxidative stress. The observed variations in metabolism parameters underline the need for study designs in pharmaco-toxicology taking into account the possible risks induced by circadian changes, especially in aged subjects.
Service de Biochimie Médicale, Faculté de Médecine Pitié-Salpêtrière, 91 boulevard de l'Hôpital, 75634 Paris Cedex 13, France.
Circadian rhythms of body temperature and motor activity were documented in young and old rats (four 8-week-old and five 22-month-old male Wistars, implanted with telemetric probes and housed in a chronobiological facility) under two different photoperiod conditions. The animals were maintained in a light:dark (LD) cycle of 12 h each (LD 12:12) for 4 weeks and then exposed to a LD 6:18 cycle for 7 weeks to assess the effect of age on the desynchronization of the temporal structure of the rhythms. In old rats under LD 12:12, the power of the 24-h component and the circadian amplitude of body temperature and motor activity were markedly lower than in the young and both rhythms were phase-advanced. After the shift to LD 6:18, the circadian rhythmicity was maintained for both variables and the same phase delay (+5+/-1 h) was observed in both age groups, as was a gradual expansion of the patterns of both functions with the longer night. The photoperiod reduction (6 weeks under LD 6:18) did not modify the power of the 24-h component of body temperature and motor activity in old rats. In young rats, however, the power and amplitude of the 24-h component of motor activity rhythm fell to the levels of those in old rats, while the power of the 24-h component of body temperature rhythm and the amplitude did not change. Our data show that the circadian rhythm of motor activity, but not of body temperature, responds age dependently to a photoperiod reduction.
Faculté de Médecine Pitié-Salpêtrière, Service de Biochimie Médicale, Paris, France.
In rodents, the alternation of light and dark is the main synchronizer of circadian rhythms. The entrainment abilities of the LD cycle could be estimated by experimental modifications of the photoperiod and by following the subsequent temporal distribution of a circadian rhythm. The rate of reentrainment of a rhythm is determined by the nature of the studied variable, by the direction (advance or delay) and the magnitude (or value) of the phase shift. In rodents, core body temperature and motor activity are known to be well synchronized with each other under L:D 12:12 and under constant conditions (LL or DD). There are clear evidences that the circadian pattern of motor activity is generated by two oscillators, one from dusk signal and the other from dawn signal. Whether the circadian rhythms of body temperature and motor activity are generated by a common circadian mechanism or controlled by separate ones still remains unknown. The purpose of this review is to summarize the results obtained on the circadian rhythms of body temperature and motor activity throughout the daily cycle in order to clarify the relationships between these two functions.
Faculté de Médecine Pitié-Salpétrière, Service de Biochimie Médicale, Paris, France.
Most biological functions present rhythmic variations. These rhythms are distinguished by their period and concern all the levels of biological life. Circadian rhythms follow a periodicity close to 24-h, they allow individuals to survive via adaptation to the periodic variations of environment. Throughout the aging process, modifications in circadian rhythms of endocrinological, metabolical and behavioural fields have been found in many animal species. This review updates the body of knowledge on aging-related alterations of the circadian rhythms of body temperature and locomotor activity: modifications in circadian profiles, modifications in the period of free-running rhythms, internal desynchronisations and modifications in entrainment ability of these rhythms.





