Does a Red House Affect Rhythms in Mice with a Corrupted Circadian System?

Menekse Öztürk,Charlotte Von Gall,Amira A H Ali,Marc Ingenwerth,Martin Sager

doi:10.3390/ijms22052288

Abstract

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.

Highlights

In mammals, many body rhythms, such as the sleep-wake cycle or hormone secretions, oscillate within a period of approximately 24 h under constant environmental conditions— this is called a circadian rhythm
Our study shows that this trade-off works well in wildtype mice with an intact light input into the circadian system and an intact molecular clockwork
In Bmal1−/− mice, which have a corrupted light input into the circadian system and a disturbed molecular clockwork, the red house (RH) has a detrimental effect on the synchronization of rhythmic spontaneous locomotor activity to the standard laboratory light/dark conditions

Summary

Introduction

Many body rhythms, such as the sleep-wake cycle or hormone secretions, oscillate within a period of approximately 24 h under constant environmental conditions— this is called a circadian rhythm. The SCN receives information about the environmental time via the retina and controls rhythmic bodily functions via the autonomous nervous system and the endocrine system Glucocorticoids such as corticosterone show a circadian fluctuation peaking at the beginning of the activity phase [2,3] and play an important role in coordinating circadian oscillators within the body. The mPER and mCRY proteins form complexes, which translocate to the nucleus and interact with CLOCK:BMAL1 heterodimers to inhibit transcription, closing the feedback loop [11]. This clockwork is present in SCN cells, and in the retina and other brain regions, as well as peripheral tissues. The retina clock [12,13] controls various aspects of retinal development and photoreceptor viability [14,15], as well as retinal physiology [16]

Methods

Results

Conclusion