Alzheimer's disease (AD) is a neurodegenerative disease often accompanied with disruption of sleep-wake cycle. The sleep-wake cycle is controlled by mechanisms involving internal timekeeping (circadian) regulation. The aim of our present pilot study was to assess the circadian system in patients with mild form of AD in their home environment. In the study, 13 elderly AD patients and 13 age-matched healthy control subjects (the patient's spouses) were enrolled. Sleep was recorded for 21 days by sleep diaries in all participants and checked by actigraphy in 4 of the AD patient/control couples. The samples of saliva and buccal mucosa were collected every 4 hours during the same 24 h-interval to detect melatonin and clock gene (PER1 and BMAL1) mRNA levels, respectively. The AD patients exhibited significantly longer inactivity interval during the 24 h and significantly higher number of daytime naps than controls. Daily profiles of melatonin levels exhibited circadian rhythms in both groups. Compared with controls, decline in amplitude of the melatonin rhythm in AD patients was not significant, however, in AD patients more melatonin profiles were dampened or had atypical waveforms. The clock genes PER1 and BMAL1 were expressed rhythmically with high amplitudes in both groups and no significant differences in phases between both groups were detected. Our results suggest moderate differences in functional state of the circadian system in patients with mild form of AD compared with healthy controls which are present in conditions of their home dwelling.

• MeSH
• aktigrafie MeSH
• Alzheimerova nemoc komplikace   patofyziologie   MeSH
• bydlení MeSH
• chorobopisy MeSH
• cirkadiánní proteiny Period biosyntéza   genetika   MeSH
• cirkadiánní rytmus fyziologie   MeSH
• lidé MeSH
• melatonin analýza   MeSH
• messenger RNA analýza   biosyntéza   MeSH
• poruchy spánku z vnitřních příčin komplikace   patofyziologie   MeSH
• regulace genové exprese MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sliny chemie   MeSH
• studie případů a kontrol MeSH
• transkripční faktory ARNTL biosyntéza   genetika   MeSH
• ústní sliznice chemie   MeSH
• životní prostředí MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The master circadian clock located in the suprachiasmatic nuclei (SCN) is dominantly entrained by external light/dark cycle to run with a period of a solar day, that is, 24 h, and synchronizes various peripheral clocks located in the body's cells and tissues accordingly. A daily restricted normocaloric feeding regime synchronizes the peripheral clocks but has no effect on SCN rhythmicity. The aim of this study was to elucidate whether feeding regime may affect the molecular mechanism generating SCN rhythmicity under conditions in which the rhythmicity is disturbed, as occurs under constant light. The rats were maintained under constant light for 30 days and were either fed ad libitum during the whole period, or their access to food was restricted to only 6 h a day during the last 2 weeks in constant light. Locomotor activity was monitored during the whole experiment. On the last day in constant light, daily expression profiles of the clock genes Per1, Per2, Bmal1, and Rev-erbα were determined in the SCN of both groups by in situ hybridization. Due to their exposure to constant light, the rats fed ad libitum became completely arrhythmic, while those exposed to the restricted feeding were active mostly during the time of food availability. In the SCN of behaviorally arrhythmic rats, no oscillations in Rev-erbα and Bmal1 gene expression were detected, but very low amplitude, borderline significant, oscillations in Per1 and Per2 persisted. Restricted feeding induced significant circadian rhythms in Rev-erbα and Bmal1 gene expression, but did not affect the low amplitude oscillations of Per1 and Per2 expression. These findings demonstrate that, under specific conditions, when the rhythmicity of the SCN is disturbed and other temporal entraining cues are lacking, the SCN molecular clockwork may likely sense temporal signals from changes in metabolic state delivered by normocaloric food.

• MeSH
• cirkadiánní proteiny Period biosyntéza   genetika   MeSH
• cirkadiánní rytmus genetika   MeSH
• fotoperioda MeSH
• hybridizace in situ MeSH
• jaderné receptory - podrodina 1, skupina D, člen 1 biosyntéza   genetika   MeSH
• krysa rodu rattus MeSH
• nucleus suprachiasmaticus fyziologie   MeSH
• potkani Wistar MeSH
• proteiny CLOCK biosyntéza   genetika   MeSH
• stanovení celkové genové exprese MeSH
• stravovací zvyklosti fyziologie   MeSH
• světlo MeSH
• transkripční faktory ARNTL biosyntéza   genetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH