Contributions of neuronal prion protein on sleep recovery and stress response following sleep deprivation.
In order to gain insights on the function of the cellular prion protein (PrP(C)) sleep and the levels of the stress hormones corticosterone (CORT) and the adrenocorticotropic hormone (ACTH) before and after sleep deprivation (SD) were compared in two wild type (WT) mice strains and the following three PrP(C) transgenic lines: mice null for PrP(C) (mPrP(0/0)) and mice with specific and central expression of PrP in neurons (NSE-HPrP/mPrP(0/0)) or in glia cells (GFAP-HPrP/mPrP(0/0)). After SD mPrP(0/0) mice showed a larger degree of sleep fragmentation and of latency to enter rapid eye movement (REM) and non-REM sleep (NREM) than WT. During sleep recovery, the amount of NREM sleep and the slow-wave activity (SWA) were reduced in mPrP(0/0) mice. After SD, CORT and ACTH levels have distinct patterns in WT and mPrP(0/0). The NREM and SWA deficit was restored in NSE-HPrP/mPrP(0/0) mice but not in GFAP-HPrP/mPrP(0/0). Hormonal profile was only partially restored in NSE-HPrP/mPrP(0/0) mice and was similar to that of mPrP(0/0) and GFAP-HPrP/mPrP(0/0) mice. These findings demonstrate that neuronal, but not non-neuronal, PrP(C) is involved in sleep homeostasis and sleep continuity. They also suggest that neuronal PrP(c)-dependent hormonal regulation of HPA axis may contribute to the sleep homeostasis.
Sánchez-Alavez
Manuel
M
Molecular and Integrative Neuroscience Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. malavez@scripps.edu
Conti
Bruno
B
Moroncini
Gianluca
G
Criado
José R
JR
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D011328:Prions / Q000235:genetics / Q000502:physiology*; D011930:Reaction Time; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D012892:Sleep Deprivation / Q000150:complications*; D013315:Stress, Psychological / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D011328:Prions; D000324:Adrenocorticotropic Hormone; D010751:Phosphopyruvate Hydratase; D003345:Corticosterone