Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB297

Poster Communications

Circadian rhythms in a rat model of depression.

E. V. Bouzinova1, S. L. Christiansen2, O. Wiborg3

1. Biomedicine, Aarhus University, Aarhus, Denmark. 2. Translational Neuropsychoatry Unit, Aarhus University, Aarhus, Denmark. 3. Health Science and Technology, Aalborg University, Aalborg, Denmark.

  • Table 1. Zeitgeber time (ZT=0 at 6:00 am) of peak and nadir expression level of clock genes in brain areas.

The circadian system plays an important role in normal physiology and its abnormal regulation can result in cardiovascular disease, metabolic syndrome, obesity, immune dysfunction, increased risk for cancer, etc. In depressed patients, specific abnormalities in circadian system are individual and might be expressed as a phase advance or phase delay of rhythms and/or increase or decrease in the amplitude (McGlung 2007). To analyse the involvement of circadian system in the development of depression, we used Wistar rats exposed for 3.5 weeks to chronic mild stress paradigm. The development of anhedonic-like behaviour was controlled weekly by sucrose consumption test and animals with more than 30% reduced sucrose intake within 3 weeks were used for further analysis. All methods and procedures are described in detail in Christiansen et al., 2016a and Christiansen et al., 2016b. We report that 3-week chronic exposure to mild stressors induces anhedonic-like behavior in some Wistar rats. Anhedonic-like rats demonstrate hypothermia (Δ=0.83oC in core body temperature at zeitgeber time (ZT) 22), hypercortisolemia (presence of the second peak at ZT2), and hypermelatoninemia (at peak ZT18 21.4 ± 1.6 vs. 15.5 ± 1.4 mmol/l (p<0.05) and at ZT22 12.2 ± 2.1 vs. 5.2 ± 1.9 mmol/l (p<0.05)). The in situ hybridization analysis of clock genes (Per1, Per2, and Bmal1) in brain slices of anhedonic-like and control rats revealed shift in phase in the expression of these genes in different brain areas (table 1). In suprachiasmatic nucleus (master clock), the expression of Per1 is sustainable in maintaining the circadian rhythm, while Per2 and Bmal1 demonstrate sensitivity to chronic stress and involvement into the development of the depression-like condition. In pineal gland, both Per1 and Bmal1 demonstrated their involvement in the development of the depression-like condition, while the expression level of Per2 was undetectable. In hippocampal areas, we were able to detect the Per1 only, which was phase-advanced in anhedonic-like rats. Thus, the normalization of the expression patterns of clock genes is likely to be essential for the recovery from the pathological depression state, induced by chronic stress. Despite the fact that mechanisms, underlying the development of depression are still under investigation, the involvement of circadian system in this process is clear and requires now a molecular biological description of the causal relationship between circadian rhythm and mood disorders. This is necessary for screening for the possible targets in order to achieve better results in the treatment of worldwide distributing pathology.

Where applicable, experiments conform with Society ethical requirements