Gene expression in the suprachiasmatic nuclei and the photoperiodic time integration.

In mammals, the 24 h-rhythmicity of many physiological events is driven by the circadian clock contained in the suprachiasmatic nuclei (SCN). In the SCN, clock gene expressions produce the rhythmicity and control the expression of clock-controlled genes which play a role in the distribution of daily messages. The daily expression of all these genes is modulated by the duration of the light phase (i.e. photoperiod). The aim of this study was first to determine if these daily changes of expression reflect a real integration of a new photoperiod by the circadian clock or reflect only a passive effect of the light. In this way, we performed a time course of the modifications of gene expression after a transfer of Syrian hamsters from long to short photoperiod (LP and SP). Our results demonstrate that the core of the SCN (clock genes) integrates quickly a new photoperiod which entrains a slow adaptation of the clock-controlled gene expressions and induces a differential daily functioning of an SCN-target tissue, the pineal gland. We next asked the question whether SCN are involved in the photorefractory phase observed in Syrian hamsters exposed to SP for 26 weeks. All genes analyzed present a similar daily expression in SP-refractory and in SP with the exception of Clock. Its particular expression in SP-refractory is different than ones observed in SP or in LP. Thus, Clock seems to play a role in the development of the photorefractory phase, or this physiological state may modify the expression of Clock in the SCN. As a conclusion, it appears that the photoperiodic time measurement involves daily modifications of the molecular functioning of the SCN and that SCN also play a role in the measurement of the duration of the time passed in a short photoperiod.

Expression of Tgfalpha in the suprachiasmatic nuclei of nocturnal and diurnal rodents.

Transforming growth factor alpha (TGFalpha) in the suprachiasmatic nuclei (SCN) has been proposed as an inhibitory signal involved in the control of daily locomotor activity. This assumption is based mainly on studies performed in nocturnal hamsters. To test whether the transcriptional regulation of Tgfalpha can be correlated with the timing of overt activity in other species, we compared Tgfalpha expression in the SCN of nocturnal Swiss mice and of diurnal Arvicanthis housed under a light/dark cycle (LD) or transferred to constant darkness (DD). In agreement with data on hamsters, Tgfalpha mRNA levels in the mouse SCN showed peak and trough levels around (subjective) dawn and dusk, respectively, roughly corresponding to the period of rest and activity in this species. In contrast, in Arvicanthis housed in DD, the circadian rhythm of SCN Tgfalpha was similar to that of the mice in spite of opposite phasing of locomotor activity. Furthermore, in Arvicanthis exposed to LD, Tgfalpha mRNA levels were constitutively high throughout the day. A tonic role of light in the regulation of Tgfalpha in Arvicanthis was confirmed by an increased expression of Tgfalpha in response to a 6-h exposure to light during daytime in animals otherwise kept in DD. In conclusion, this study shows that, contrary to what is observed in mice, Tgfalpha mRNA levels in the SCN of Arvicanthis do not match timing of locomotor activity and are modulated by light.

Photoperiod differentially regulates clock genes' expression in the suprachiasmatic nucleus of Syrian hamster.

The suprachiasmatic nuclei (SCN) contain the master circadian pacemaker in mammals. Generation and maintenance of circadian oscillations involve clock genes which interact to form transcriptional/translational loops and constitute the molecular basis of the clock. There is some evidence that the SCN clock can integrate variations in day length, i.e. photoperiod. However, the effects of photoperiod on clock-gene expression remain largely unknown. We here report the expression pattern of Period (Per) 1, Per2, Per3, Cryptochrome (Cry) 1, Cry2, Bmal1 and Clock genes in the SCN of Syrian hamsters when kept under long (LP) and short (SP) photoperiods. Our data show that photoperiod differentially affects the expression of all clock genes studied. Among the components of the negative limb of the feedback loop, Per1, Per2, Per3, Cry2 but not Cry1 genes show a shortened duration of their peak expression under SP compared with LP. Moreover, mRNA expression of Per1, Per3 and Cry1 are phase advanced in SP compared with LP. Per3 shows an mRNA peak of higher amplitude under SP conditions whereas Per1 and Per2 peak amplitudes are unaffected by photoperiod changes. Bmal1 expression is phase advanced without a change of duration in SP compared with LP. Furthermore, the expression of Clock is rhythmic under SP whereas no rhythm is observed under LP. These results, which provide further evidence that the core clock mechanisms of the SCN integrate photoperiod, are discussed in the context of the existing molecular model.