Lithium is regarded as a unique therapeutic agent for the management of bipolar disorder (BD). In efforts to explain the favourable effects of lithium in BD, a wide range of mechanisms was suggested. Among those, the effect of clinically relevant concentrations of lithium on the plasma membrane was extensively studied. However, the biophysical properties of brain membranes isolated from experimental animals exposed to acute, short-term and chronic lithium have not been performed to-date. In this study, we compared the biophysical parameters and level of lipid peroxidation in membranes isolated from forebrain cortex (FBC) of therapeutic lithium-treated and/or sleep-deprived rats. Lithium interaction with FBC membranes was characterized by appropriate fluorescent probes. DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH (1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulphonate) were used for characterization of the hydrophobic lipid core and Laurdan (6-dodecanoyl-2-dimethylaminonaphthalene) for the membrane-water interface. Lipid peroxidation was determined by immunoblot analysis of 4-HNE-(4-hydroxynonenal)-protein adducts. The organization of polar head-group region of FBC membranes, measured by Laurdan generalized polarization, was substantially altered by sleep deprivation and augmented by lithium treatment. Hydrophobic membrane interior characterized by steady-state anisotropy of DPH and TMA-DPH fluorescence was unchanged. Chronic lithium had a protective effect against peroxidative damage of membrane lipids in FBC. In summary, lithium administration at a therapeutic level and/or sleep deprivation as an animal model of mania resulted in changes in rat FBC membrane properties.
- MeSH
- fluidita membrány účinky léků MeSH
- krysa rodu rattus MeSH
- lipidové dvojvrstvy metabolismus MeSH
- lithium farmakologie MeSH
- membránové lipidy metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- přední mozek účinky léků metabolismus MeSH
- spánková deprivace metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lithium (Li) is a typical mood stabilizer and the first choice for treatment of bipolar disorder (BD). Despite an extensive clinical use of Li, its mechanisms of action remain widely different and debated. In this work, we studied the time-course of the therapeutic Li effects on ouabain-sensitive Na+/K+-ATPase in forebrain cortex and hippocampus of rats exposed to 3-day sleep deprivation (SD). We also monitored lipid peroxidation as malondialdehyde (MDA) production. In samples of plasma collected from all experimental groups of animals, Li concentrations were followed by ICP-MS. The acute (1 day), short-term (7 days) and chronic (28 days) treatment of rats with Li resulted in large decrease of Na+/K+-ATPase activity in both brain parts. At the same time, SD of control, Li-untreated rats increased Na+/K+-ATPase along with increased production of MDA. The SD-induced increase of Na+/K+-ATPase and MDA was attenuated in Li-treated rats. While SD results in a positive change of Na+/K+-ATPase, the inhibitory effect of Li treatment may be interpreted as a pharmacological mechanism causing a normalization of the stress-induced shift and return the Na+/K+-ATPase back to control level. We conclude that SD alone up-regulates Na+/K+-ATPase together with increased peroxidative damage of lipids. Chronic treatment of rats with Li before SD, protects the brain tissue against this type of damage and decreases Na+/K+-ATPase level back to control level.
- MeSH
- antimanika farmakologie terapeutické užití MeSH
- hipokampus účinky léků metabolismus MeSH
- kompetitivní vazba účinky léků MeSH
- krysa rodu rattus MeSH
- lithiumkarbonát farmakologie MeSH
- malondialdehyd metabolismus MeSH
- ouabain metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- potkani Wistar MeSH
- přední mozek účinky léků enzymologie metabolismus MeSH
- sodíko-draslíková ATPasa metabolismus MeSH
- spánková deprivace farmakoterapie enzymologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aging and chronic sleep deprivation (SD) are well-recognized risk factors for Alzheimer's disease (AD), with N-methyl-D-aspartate receptor (NMDA) and downstream nitric oxide (NO) signalling implicated in the process. Herein, we investigate the impact of the age- and acute or chronic SD-dependent changes on the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) and on the activities of NO synthase (NOS) isoforms in the cortex of Wistar rats, with reference to cerebral lateralization. In young adult controls, somewhat lateralized seasonal variations in neuronal and endothelial NOS have been observed. In aged rats, overall decreases in NR1, NR2A, and NR2B expression and reduction in neuronal and endothelial NOS activities were found. The age-dependent changes in NR1 and NR2B significantly correlated with neuronal NOS in both hemispheres. Changes evoked by chronic SD (dysfunction of endothelial NOS and the increasing role of NR2A) differed from those evoked by acute SD (increase in inducible NOS in the right side). Collectively, these results demonstrate age-dependent regulation of the level of NMDA receptor subunits and downstream NOS isoforms throughout the rat brain, which could be partly mimicked by SD. As described herein, age and SD alterations in the prevalence of NMDA receptors and NOS could contribute towards cognitive decline in the elderly, as well as in the pathobiology of AD and the neurodegenerative process.
- MeSH
- Alzheimerova nemoc epidemiologie etiologie MeSH
- krysa rodu rattus MeSH
- membránové glykoproteiny genetika metabolismus MeSH
- mozková kůra metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- receptory N-methyl-D-aspartátu genetika metabolismus MeSH
- regulace genové exprese MeSH
- rizikové faktory MeSH
- signální transdukce * MeSH
- spánková deprivace metabolismus patofyziologie MeSH
- stárnutí metabolismus MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Obesity is linked to a wide range of serious illnesses. In addition to the important impact on the health of the individual, obesity also has a substantial impact on the economy. Disruption of physiological day-night cycles could contribute to the increased incidence of obesity. According to the American National Sleep Federation, the percentage of the people who reported a sleep duration of six hours or less increased from 12 to 37 % over ten years. Insufficient sleep leads not only to an increase of the total calorie intake but changes the meal preference in favor of palatable foods and meals with high carbohydrate content. A decrease of leptin and increase of ghrelin levels caused by sleep deficiency can also play a role. In addition to the higher caloric intake, the timing of food consumption should be taken into account. The same meal eaten during the night versus the day is associated with increased postprandial glucose and triglyceride levels. The gut microbiome has also been recently understood as an endocrine system, with links between the gut microbiome and circadian rhythm changes possibly influencing increased obesity.
- MeSH
- cirkadiánní rytmus fyziologie MeSH
- energetický příjem fyziologie MeSH
- lidé MeSH
- obezita komplikace metabolismus mikrobiologie MeSH
- postprandiální období fyziologie MeSH
- spánková deprivace komplikace metabolismus mikrobiologie MeSH
- střevní mikroflóra fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Syndrom obstrukční spánkové apnoe (OSA) je u diabetiků 2. typu velmi časté onemocnění, které významně zvyšuje kardiovaskulární morbiditu i mortalitu. OSA byla řadou studií identifikována jako nezávislý rizikový faktor rozvoje inzulinové rezistence, glukózové intolerance a diabetes mellitus 2. typu. Porucha glukózové homeostázy u pacientů s OSA je pravděpodobně zprostředkována chronickou intermitentní hypoxií nebo spánkovou fragmentací skrze aktivaci sympatického nervového systému, hypotalamo-hypofyzární-adrenální osy, prozánětlivých drah či oxidačního stresu. Navzdory vysoké prevalenci OSA mezi diabetiky 2. typu i prokázanému benefitu léčby kontinuálním pozitivním přetlakem (CPAP) na redukci mortality zůstává většina pacientů s OSA nediagnostikovaná. Na místě je proto provádění aktivního screeningu OSA u všech diabetiků 2. typu nejlépe pomocí domácí monitorace saturace a dýchání ve spánku. Ačkoli efekt léčby CPAP na zlepšení kompenzace cukrovky (snížení glykovaného hemoglobinu) nebyl u diabetiků 2. typu zatím jednoznačně prokázán, byly zaznamenány slibné výsledky při léčbě pacientů s prediabetem.
Obstructive sleep apnoea syndrome (OSA) is a disease very frequently occurring in people with type 2 diabetes, that significantly increases cardiovascular morbidity and mortality. In a number of studies, OSA has been identified as an independent risk factor for the development of insulin resistance, glucose intolerance and type 2 diabetes mellitus. Disorders of glucose homeostasis in patients with OSA are probably mediated by chronic intermittent hypoxia and/or sleep fragmentation through activation of the sympathetic nervous system, the hypothalamic-pituitary-adrenal stress axis, pro-inflammatory paths or oxidative stress. Despite the high prevalence of OSA among patients with type 2 diabetes as well as the proven benefit of the continuous positive airway pressure (CPAP) therapy on reduction of mortality, most patients with OSA remain undiagnosed. Active OSA screening should therefore be performed in all patients with type 2 diabetes, ideally through home monitoring of oxygen saturation and breathing during sleep. Although the effect of CPAP therapy on the improvement in diabetes control (decrease in glycated hemoglobin) has not been clearly proven in patients with type 2 diabetes so far, promising outcomes have been observed during the treatment of patients with prediabetes.
- Klíčová slova
- intermitentní hypoxie,
- MeSH
- diabetes mellitus 2. typu * diagnóza mortalita MeSH
- hypoxie buňky fyziologie MeSH
- komplikace diabetu MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- obstrukční spánková apnoe * diagnóza terapie MeSH
- prevalence MeSH
- rizikové faktory MeSH
- spánková deprivace komplikace metabolismus patologie MeSH
- trvalý přetlak v dýchacích cestách přístrojové vybavení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- diabetes mellitus 2. typu * etiologie metabolismus prevence a kontrola MeSH
- energetický metabolismus MeSH
- hmotnostní přírůstek MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- obezita * etiologie metabolismus prevence a kontrola MeSH
- přijímání potravy MeSH
- rizikové faktory MeSH
- spánková deprivace * komplikace metabolismus patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- chronobiologické jevy MeSH
- chuť k jídlu MeSH
- cirkadiánní rytmus MeSH
- diabetes mellitus 2. typu * etiologie MeSH
- inzulinová rezistence MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- metabolický syndrom etiologie metabolismus MeSH
- obezita etiologie metabolismus MeSH
- poruchy metabolismu glukózy etiologie MeSH
- rizikové faktory MeSH
- spánek fyziologie MeSH
- spánková deprivace * metabolismus patofyziologie MeSH
- vliv směnného provozu na zdraví fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- adrenokortikotropní hormon fyziologie imunologie metabolismus MeSH
- buněčná imunita genetika účinky léků MeSH
- chuť k jídlu fyziologie imunologie MeSH
- cytokiny fyziologie imunologie metabolismus MeSH
- endokrinní systém fyziologie imunologie MeSH
- financování organizované MeSH
- hormon uvolňující kortikotropin fyziologie imunologie metabolismus MeSH
- imunitní systém fyziologie imunologie MeSH
- lidé MeSH
- metabolismus fyziologie imunologie MeSH
- neuropeptidy fyziologie imunologie metabolismus MeSH
- růstový hormon fyziologie imunologie metabolismus MeSH
- spánková deprivace imunologie komplikace metabolismus MeSH
- thyreotropin fyziologie imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
