Neuromedin‐U is regulated by the circadian clock in the SCN of the mouse

Mar 1, 2005The European journal of neuroscience

Daily Clock Controls Neuromedin-U Levels in the Mouse Brain's Timekeeping Center

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Abstract

Neuromedin-U (NMU) shows a circadian expression pattern with peak levels during the light phase.

NMU expression peaks in the light phase of a light-dark cycle.
In constant darkness, NMU rhythms align with the free running period of locomotor activity in C3H mice.
NMU mRNA transcripts colocalize with cells expressing vasopressin (AVP) in the suprachiasmatic nucleus (SCN).
NMU and AVP exhibit coincident rhythmic expression.
Corticotropin-releasing factor (CRF) does not show a circadian rhythm in a light-dark cycle, but does in constant darkness.
The timing of CRF expression peaks before NMU levels rise, suggesting NMU does not drive the circadian rhythm of CRF.

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Neuromedin-U (NMU) has been reported to drive several physiological or behavioural responses following i.c.v. injection of the peptide into the third ventricle of rodent brains. Many of these responses are mediated through a change in corticotrophin-releasing factor (CRF) output from the paraventricular nucleus (PVN). A number of the physiological or behavioural responses are regulated in a circadian manner, e.g. feeding. We have previously reported NMU gene expression in the suprachiasmatic nucleus (SCN) and NMU-2 receptor expression in the PVN, dorsal medial hypothalamus (DMH) and other regions of the mouse brain. We therefore hypothesized that NMU would be regulated by the circadian clock and may consequently drive a circadian rhythm of CRF expression in the PVN. Here we report that NMU is regulated in a circadian manner with peak expression during the light phase of a light-dark cycle. In C3H mice held in constant darkness, the NMU rhythm free runs with a period predicted by the free running period of locomotor activity in this mouse. The NMU mRNA transcript colocalizes with cells expressing AVP in the SCN and shows a coincident rhythm of expression with AVP. On the other hand, CRF did not express a circadian rhythm of expression in a light-dark cycle, although a rhythm was evident in constant darkness with a peak of expression prior to the rise of NMU in the same conditions. This would suggest that the circadian rhythm in NMU expression in the SCN does not drive a circadian rhythm in CRF in the PVN to be translated into physiological and behavioural responses mediated by NMU.

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Neuromedin‐U is regulated by the circadian clock in the SCN of the mouse

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