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Published on: September 28, 2017
Behavioral characterization and modulation of circadian rhythms by light and melatonin in C3H/HeN mice homozygous for
Monica I Masana1, Isabel C Sumaya, Michael Becker-Andre
1Department of Molecular Pharmacology and Biological Chemistry Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3008, USA.
Abstract:
This study reports for the first time the effects of retinoid-related orphan receptors [RORbeta; receptor gene deletion RORbeta(C3H)(-/-)] in C3H/HeN mice on behavioral and circadian phenotypes. Pineal melatonin levels showed a robust diurnal rhythm with high levels at night in wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice. The RORbeta(C3H)(-/-) mice displayed motor ("duck gait," hind paw clasping reflex) and olfactory deficits, and reduced anxiety and learned helplessness-related behaviors. Circadian rhythms of wheel-running activity in all genotypes showed entrainment to the light-dark (LD) cycle, and free running in constant dark, with RORbeta(C3H)(-/-) mice showing a significant increase in circadian period (tau). Melatonin administration (90 microg/mouse sc for 3 days) at circadian time (CT) 10 induced phase advances, while exposure to a light pulse (300 lux) at CT 14 induced phase delays of circadian activity rhythms of the same magnitude in all genotypes. In RORbeta(C3H)(-/-) mice a light pulse at CT 22 elicited a larger phase advance in activity rhythms and a slower rate of reentrainment after a 6-h advance in the LD cycle compared with (+/+) mice. Yet, the rate of reentrainment was significantly advanced by melatonin administration at the new dark onset in both (+/+) and (-/-) mice. We conclude that the RORbeta nuclear receptor is not involved in either the rhythmic production of pineal melatonin or in mediating phase shifts of circadian rhythms by melatonin, but it may regulate clock responses to photic stimuli at certain time domains.
Insights
Retinoid-related orphan receptor beta (RORbeta) gene deletion in mice impacts motor and olfactory functions, and anxiety. While not affecting melatonin rhythms, RORbeta influences circadian clock responses to light.
Area of Science:
- Neuroscience
- Chronobiology
- Genetics
Background:
- Retinoid-related orphan receptors (RORs) are nuclear receptors involved in various biological processes.
- RORbeta's role in behavioral and circadian phenotypes remains largely unexplored.
Purpose of the Study:
- To investigate the effects of RORbeta gene deletion on behavioral and circadian phenotypes in C3H/HeN mice.
Main Methods:
- Generation of RORbeta knockout mice (RORbeta(C3H)(-/-)).
- Assessment of behavioral phenotypes (motor, olfactory, anxiety, learned helplessness).
- Analysis of circadian activity rhythms, melatonin levels, and responses to light and melatonin stimuli.
Main Results:
- RORbeta(C3H)(-/-) mice exhibited motor deficits (duck gait, hind paw clasping) and olfactory deficits.
- These mice showed reduced anxiety and learned helplessness behaviors.
- Circadian period (tau) was significantly increased in RORbeta(C3H)(-/-) mice.
- While melatonin production was unaffected, RORbeta deletion altered responses to light stimuli at specific circadian times.
Conclusions:
- RORbeta is not essential for rhythmic pineal melatonin production or melatonin-mediated phase shifts.
- RORbeta plays a role in regulating clock responses to photic stimuli, particularly at late circadian times.
- RORbeta influences motor, olfactory, and anxiety-related behaviors.
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