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The circadian rhythms of body functions in mammals are controlled by the circadian system. The suprachiasmatic nucleus (SCN) in the hypothalamus orchestrates subordinate oscillators. Time information is conveyed from the retina to the SCN to coordinate an organism's physiology and behavior with the light/dark cycle. At the cellular level, molecular clockwork composed of interlocked transcriptional/translational feedback loops of clock genes drives rhythmic gene expression. Mice with targeted deletion of the essential clock gene Bmal1 (Bmal1-/-) have an impaired light input pathway into the circadian system and show a loss of circadian rhythms. The red house (RH) is an animal welfare measure widely used for rodents as a hiding place. Red plastic provides light at a low irradiance and long wavelength-conditions which affect the circadian system. It is not known yet whether the RH affects rhythmic behavior in mice with a corrupted circadian system. Here, we analyzed whether the RH affects spontaneous locomotor activity in Bmal1-/- mice under standard laboratory light conditions. In addition, mPER1- and p-ERK-immunoreactions, as markers for rhythmic SCN neuronal activity, and day/night plasma corticosterone levels were evaluated. Our findings indicate that application of the RH to Bmal1-/- abolishes rhythmic locomotor behavior and dampens rhythmic SCN neuronal activity. However, RH had no effect on the day/night difference in corticosterone levels.

Background: The astroglial connexins Cx30 and Cx43 contribute to many important CNS functions including cognitive behaviour, motoric capacity and regulation of the sleep-wake cycle. The sleep wake cycle, is controlled by the circadian system. The central circadian rhythm generator resides in the suprachiasmatic nucleus (SCN). SCN neurons are tightly coupled in order to generate a coherent circadian rhythm. The SCN receives excitatory glutamatergic input from the retina which mediates entrainment of the circadian system to the environmental light-dark cycle. Connexins play an important role in electric coupling of SCN neurons and astrocytic-neuronal signalling that regulates rhythmic SCN neuronal activity. However, little is known about the regulation of Cx30 and Cx43 expression in the SCN, and the role of these connexins in light entrainment of the circadian system and in circadian rhythm generation., Methods: We analysed time-of-day dependent as well as circadian expression of Cx30 and Cx43 mRNA and protein in the mouse SCN by means of qPCR and immunohistochemistry. Moreover, we analysed rhythmic spontaneous locomotor activity in mice with a targeted deletion of Cx30 and astrocyte specific deletion of Cx43 (DKO) in different light regimes by means of on-cage infrared detectors., Results: Fluctuation of Cx30 protein expression is strongly dependent on the light-dark cycle whereas fluctuation of Cx43 protein expression persisted in constant darkness. DKO mice entrained to the light-dark cycle. However, re-entrainment after a phase delay was slightly impaired in DKO mice. Surprisingly, DKO mice were more resilient to chronodisruption., Conclusion: Circadian fluctuation of Cx30 and Cx43 protein expression in the SCN is differently regulated. Cx30 and astroglial Cx43 play a role in rhythm stability and re-entrainment under challenging conditions.

Circadian disruption is associated with the development of diabetes. Non-obese diabetic (NOD) mice show abnormal diurnal profiles in energy balance and locomotor activity suggesting circadian misalignment. Therefore, we analyzed cFos and mPER1 as markers for rhythmic neuronal activity within the suprachiasmatic nucleus (SCN) of wildtype (WT) and non-diabetic (nNOD) as well as acutely diabetic NOD (dNOD) mice. cFos levels show a day/night difference in both WT and nNOD but not in dNOD. mPER1 levels did not show a day/night difference in both nNOD and dNOD. This suggests that disruption of SCN rhythmicity in NOD mice precedes the actual onset of diabetes.