October 28, 2013

expert reaction to a neuropeptide, cellular synchrony and jet lag in mice

 A study in PNAS found that mice were able to adjust to a new time zone more quickly if they had been given an injection of a neuropeptide the previous day.

Dr Jonathan Johnston, Reader in Chronobiology and Integrative Physiology, University of Surrey, said:

“The body’s master clock is found in a part of the brain called the SCN (suprachiasmatic nuclei).  We have known for many years that VIP (vasoactive intestinal polypeptide) is a signalling molecule, which synchronises rhythms in individual cells of the SCN.  What is really interesting about this study is that high doses of VIP actually seem to have an opposite effect and in fact desynchronise SCN cells.  This desynchronised state allows the SCN clock to respond more quickly to a jet-lag situation.

“It is unclear whether this finding could be used to minimise jet lag symptoms in humans.  First, VIP is used by other parts of the body and so a drug would need to be specific to the SCN.  Second, jet lag symptoms are thought to result from other clocks in the body responding more slowly than the SCN to a new time zone.  It would therefore be more important to help these other clocks respond faster.”

Dr Michael Hastings, Group Leader in Circadian Neurobiology, MRC Laboratory of Molecular Biology, said:

“The study by Herzog et al builds on previous work by several groups showing that VIP is important for holding the individual clock cells of the SCN (the brain’s master circadian clock) in synchrony.  Thus whereas before too little VIP was shown to be a bad thing (disrupted clock) now Herzog et al show too much can also loosen the clockwork.  They then show that such a loose clock can adjust to altered time zones more rapidly.  There are many parallels between this paper and a recent paper in Science (Yamaguchi et al, Science 2013; see Hastings, Science 2013 for commentary).  The Yamaguchi paper showed that in mice lacking receptors to another SCN neuropeptide, AVP, the clock is looser and more reactive to time zone shifts.

“Both the Yamaguchi paper and this new (Herzog) paper have built upon existing knowledge about the role of neuropeptides in clock synchrony to develop an unusual condition where cell to cell links are weakened and then they show in both cases a more rapid re-adjustment i.e. lack of “jet-lag”.  They both use mouse experimental models but there is every reason to expect the findings are transferrable to humans – we have the same peptides and clock cells as do mice.

“Both studies face common issues for translational development.  First, compounds to treat the SCN based on peptidergic signalling will need access to the brain, and second, they must be tailored to alter SCN functions and avoid side effects – the likelihood of side effects is very high because both VIP and AVP perform important vital functions elsewhere in the nervous and endocrine systems.”

‘A neuropeptide speeds circadian entrainment by reducing intercellular synchrony’ by Sungwon An et al. published in PNAS on Monday 28 October 2013.