Disrupted circadian rhythms in VIP- and PHI-deficient mice.

[Guest guest]

Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R939-49. Epub 2003

Jul 10.

Disrupted circadian rhythms in VIP- and PHI-deficient mice.

Colwell CS, Michel S, Itri J, W, Tam J, Lelievre V, Hu Z, Liu X,

Waschek JA.

Mental Retardation Res. Ctr., Univ. of California - Los Angeles, 760

Westwood Plaza, Los Angeles, CA 90024-1759, USA. ccolwell@...

The related neuropeptides vasoactive intestinal peptide (VIP) and peptide

histidine isoleucine (PHI) are expressed at high levels in the neurons of

the suprachiasmatic nucleus (SCN), but their function in the regulation of

circadian rhythms is unknown. To study the role of these peptides on the

circadian system in vivo, a new mouse model was developed in which both VIP

and PHI genes were disrupted by homologous recombination.

In a light-dark cycle, these mice exhibited diurnal rhythms in activity

which were largely indistinguishable from wild-type controls. In constant

darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in

their circadian system. The activity patterns started approximately 8 h

earlier than predicted by the previous light cycle. In addition, lack of

VIP/PHI led to a shortened free-running period and a loss of the coherence

and precision of the circadian locomotor activity rhythm.

In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm

became arrhythmic after several weeks in constant darkness. Another striking

example of these deficits is seen in the split-activity patterns expressed

by the mutant mice when they were exposed to a skeleton photoperiod.

In addition, the VIP/PHI-deficient mice exhibited deficits in the response

of their circadian system to light. Electrophysiological analysis indicates

that VIP enhances inhibitory synaptic transmission within the SCN of

wild-type and VIP/PHI-deficient mice.

Together, the observations suggest that VIP/PHI peptides are critically

involved in both the generation of circadian oscillations as well as the

normal synchronization of these rhythms to light.

PMID: 12855416 [PubMed - in process]

_________________________________________________________________

Cell phone ‘switch’ rules are taking effect — find out more here.

http://special.msn.com/msnbc/consumeradvocate.armx