The physiological function of the pancreas is controlled by the circadian clock. The aim of this study was to determine whether aging-induced changes in glucose homeostasis affect properties of the circadian clock in the pancreas and/or its sensitivity to disturbances in environmental lighting conditions. mPer2Luc mice aged 24-26 months developed hyperinsulinemic hypoglycaemia, which was likely due to the Pclo-mediated insulin hyper-secretion and Slc2a2-mediated glucose transport impairment in the pancreas, and due to the alterations in Pp1r3c-related glycogen storage and Sgk1-related glucose transport in the liver. In the pancreatic tissue, aging affected clock gene expression only marginally, it upregulated Bmal1 and downregulated Clock expression. Whereas aging significantly impaired the circadian clock in lung explants, which were used as a control tissue, the properties of the pancreatic clock in vitro were not affected. The data suggest a non-circadian role of Bmal1 in changes of pancreatic function that occur during aging. Additionally, the pancreatic clock was more sensitive to exposure of animals to constant light conditions. These findings provide an explanation for the previously demonstrated relationship between disturbances in the circadian system and disordered glucose homeostasis, including diabetes mellitus type 2, in subjects exposed to long-term shift work.
- MeSH
- cirkadiánní hodiny * účinky záření MeSH
- cirkadiánní proteiny Period metabolismus MeSH
- glukosa metabolismus MeSH
- homeostáza * MeSH
- játra metabolismus MeSH
- kolon metabolismus MeSH
- myši MeSH
- orgánová specificita genetika MeSH
- pankreas metabolismus účinky záření MeSH
- proteiny CLOCK genetika metabolismus MeSH
- regulace genové exprese účinky záření MeSH
- stárnutí metabolismus MeSH
- světlo MeSH
- transkripční faktory ARNTL genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Circadian regulation of behavior worsens with age, however, the mechanism behind this phenomenon is still poorly understood. Specifically, it is not clear to what extend the ability of the circadian clock in the suprachiasmatic nuclei (SCN) to generate the rhythm is affected by aging. This study aimed to ascertain the effect of aging on the functioning of the SCN of mPer2Luciferasemice under unnatural lighting conditions, such as constant light (LL). Under LL, which worsened the age-induced effect on behavioral rhythms, a marginal age-dependent effect on in vitro rhythmicity in explants containing the middle, but not the rostral/caudal, regions of the SCN was apparent; the proportion of mice in which middle-region SCN explants were completely arrhythmic or had an extremely long period (>30 h) was 47% in aged mice and 27% in adults. The results suggest that in some of the aged animals, LL may weaken the coupling among oscillators in specific sub-regions of the SCN, leaving other sub-regions better synchronized. In the standard light/dark cycle and in constant darkness, the SCN ability to produce bioluminescence rhythms in vitro was not compromised in aged mice although aging significantly affected their SCN-driven locomotor activity rhythms. Therefore, our results demonstrate that although age worsened the SCN output rhythm, the SCN molecular core clock mechanism itself was relatively resilient to aging in these same animals. The results suggest the involvement of pathways downstream of the core clock mechanism which are responsible for this phenomenon.
- MeSH
- chování zvířat fyziologie MeSH
- cirkadiánní proteiny Period genetika metabolismus MeSH
- cirkadiánní rytmus fyziologie MeSH
- fotoperioda * MeSH
- luciferasy MeSH
- myši knockoutované MeSH
- myši MeSH
- nucleus suprachiasmaticus fyziologie MeSH
- pohybová aktivita MeSH
- regulace genové exprese fyziologie MeSH
- stárnutí fyziologie MeSH
- světlo * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Colonic function is controlled by an endogenous clock that allows the colon to optimize its function on the daytime basis. For the first time, this study provided evidence that the clock is synchronized by rhythmic hormonal signals. In rat colon, adrenalectomy decreased and repeated applications of dexamethasone selectively rescued circadian rhythm in the expression of the clock gene Per1. Dexamethasone entrained the colonic clock in explants from mPer2Lucmice in vitro. In contrast, pinealectomy had no effect on the rat colonic clock, and repeated melatonin injections were not able to rescue the clock in animals maintained in constant light. Additionally, melatonin did not entrain the clock in colonic explants from mPer2Lucmice in vitro. However, melatonin affected rhythmic regulation of Nr1d1 gene expression in vivo. The findings provide novel insight into possible beneficial effects of glucocorticoids in the treatment of digestive tract-related diseases, greatly exceeding their anti-inflammatory action.
- MeSH
- cirkadiánní hodiny fyziologie MeSH
- cirkadiánní proteiny Period genetika metabolismus MeSH
- epifýza mozková chirurgie MeSH
- fotoperioda * MeSH
- inbrední kmeny myší MeSH
- kolon fyziologie MeSH
- krysa rodu rattus MeSH
- mutace MeSH
- myši MeSH
- nadledviny chirurgie MeSH
- potkani Wistar MeSH
- regulace genové exprese fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Poruchy kognitívnych funkcií sa vyskytujú približne u 65 % patientov so sclerosis multiplex (SM). Sluchové kognitívne evokované potenciály (ERP), hlavne vlna P300, sú objektívnym elektrofyziologickým ukazovateľom kognitívnych funkcií. Cieľom práce bolo zistiť výskyt kognitívnych porúch u pacientov so SM pomocou sluchových kognitívnych evokovaných potenciálov a porovnať ich s demografickými a klinickými dátami chorých. Súbor pacientov a metodika: Autori vyšetrili 110 pacientov s definitívnou diagnózou SM (60 s relapso-remitujúcou, 41 so sekundárne progresívnou a 9 s primárne progresívnou formou SM) a 130 osôb kontrolnej skupiny. Výsledky ERP boli porovnané so stupňom funkčného zneschopnenia vyjadreným pomocou Kurtzkého stupnice EDSS (Expanded Disability Status Scale), stupňom kognitívnych porúch v psychometrických testoch, rozsahom chorobnej únavy, depresie a kvalitou života chorých. Výsledky: Latencie vlny N200 a P300 boli patologicky predĺžené v 69 % prípadov pacientov v porovnaní s kontrolami; bola nájdená zvýšená hodnota amplitúdy vlny P300. Predĺženie latencie vlny P300 vysoko korelovalo s kognitívnymi poruchami v psychometrickom teste (Grassiho test organicity), skóre v stupnici únavy a kvality života. Nízke korelácie sa zistili vo vzťahu k veku pacienta, trvaniu ochorenia, stupňu EDSS, skóre v Mini-Mental-State-Examination a IQ (hodnotené testom Ravenových progresívnych matríc). Kognitívny deficit nekoreloval so stupňom depresie chorých. Pacienti s progresívnymi formami (primárne a sekundárne progresívna) vykazovali výraznejší kognitívny deficit v porovnaní s relapso?remitujúcou formou ochorenia. Záver: Kognitívny deficit sa vyskytuje v našom súbore u 69 % pacientov. Súvisí s chorobnou únavou a negatívne ovplyvňuje kvalitu života chorých. Deficit je výraznejší u progresívnych foriem SM a v priebehu ochorenia narastá. Sluchové kognitívne evokované potenciály, vlna P300, sú vhodnou metódou vyšetrenia a monitoringu kognitívnych porúch u sclerosis multiplex.
- MeSH
- alkoholismus diagnóza MeSH
- dospělí MeSH
- epilepsie diagnóza etiologie MeSH
- intrakraniální krvácení diagnóza etiologie MeSH
- ischemie mozku diagnóza etiologie MeSH
- lidé MeSH
- mozková angiografie metody MeSH
- nemoci nervového systému diagnóza etiologie MeSH
- vertebrobazilární insuficience diagnóza etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
