NR ABSC
AU Brown,D.R.
TI Don't lose sleep over prions: role of prion protein in sleep regulation.
QU Neuroreport 2002 Jan 21; 13(1): A1
PT journal article
VT
The prion protein's abnormal isoform is the acknowledge cause of the infamous prion diseases such as BSE and CJD. However, a growing body of literature suggests that the normal isoform of the prion protein (PrPc) expressed in the brains of all vertebrates is beneficial and serves a useful purpose [1]. PrPc is a copper binding protein with a possible anti-oxidant function. Insights into the normal function of the PrPc and its essential role in the nervous system have emerged from continuing studies of PrP-knockout mice originally developed in the laboratories of Charles Weissmann [2] and Jean Manson [3]. Although PrP-knockout mice appear to develop normally and show no gross behavioural disturbances they have differences wild-type mice. The group of Irene Tobler has focused for some years now on the role of PrPc in circadian rhythms and sleep regulation. Their original findings [4] published in 1996 in Nature indicated that PrP-knockout mice had a different circadian rhythm and that their periods of brief awakening during a sleep cycle was increased. This study of sleep regulation was extended by the group in 1997 in an article published in the Journal of Neuroscience [5]. Sleep deprivation was shown to have different affects on PrP-knockout mice. In particular a change in slow-wave activity (SWA) prior to sleep-wake transitions was detected in the PrP-knockout mice following sleep deprivation. These finding suggested that loss of PrPc disturbs sleep continuity. In the new study which appears in this issue of Neuroreport the Tobler group provides evidence that the prolonged SWA that occurs in periods of non-rapid eye movement sleep (NREM) in PrP-knockout mice is region specific. This indicates that regions of the brain such as the frontal cortex are unaffected by loss of PrPc expression in terms of sleep regulation. This suggests that the loss of PrPc expression does not alter sleep per se but instead the changes in brain activity during sleep reflect differences in the need of that brain region to recover from stress endured because of sleep deprivation. As sleep deprivation leads to increase oxidative stress the observations reported by the group suggests either that the occipital cortex is more stressed by the lack of sleep in the absence of the protective effects of PrPc or that, in the absence of PrPc expression, that region takes longer to recover during the sleep period. Either way this report is the first to link together two of the main hypotheses concerning PrPc function based on studies of PrP-knockout mice, namely that PrPc is an antioxidant [6] and that loss of PrPc expression disturbs brain activity [7]. Additionally, this report opens an intriguing avenue of exploration that might bring us greater insights into the importance of sleep to the regulation of brain activity.
REFERENCES
1. Brown D.R. Trends Neurosci 24, 85-90 (2001).
2. Büeler H. et al. Nature 356, 577-582 (1992).
3. Manson J.C. et al. Mol Neurobiol 8, 121-127 (1994).
4. Tobler I. et al. Nature 380, 639-642 (1996).
5. Tobler I. et al. J Neurosci 17, 1869-1879 (1997).
6. Brown D.R. et al. Biochem J 344, 1-5 (1999).
7. Collinge J. et al. Nature 370, 295-297 (1994).
AD David R. Brown, Department of Biology and Biochemistry,University of Bath, Bath, BA2 7AY,UK
SP englisch