Browsing by Subject "Circadian system"

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    Circadian activity rhythms during the last days of Nothobranchius rachovii’s life: A descriptive model of circadian system breakdown
    (Informa Healthcare USA, Inc., 2014-11-25) Lucas-Sánchez, Alejandro; Martínez-Nicolás, Antonio; Madrid, Juan Antonio; Almaida Pagán, Pedro Francisco; Mendiola, Pilar; Costa, Jorge de; Fisiología
    Several studies have been performed to identify age-related changes in the circadian system (CS) but the impairment of the CS and its chronodisruption at the end of an organism life have not been studied in depth. Aging commonly affects the input pathways into the biological clock or restraints their processing, therefore simplifying the system output, the overt rhythms. The purpose of this work was to do a complete characterization of changes that occurs in the CS in the last stage of a vertebrate organism life and to develop tools able to detect in which moment of the last days of life is the animal, using an overt rhythm, the rest-activity rhythm (RAR). For that, a fish species proposed as model for aging studies, Nothobranchius rachovii, has been used. A progressive and sequential CS breakdown has been described for the last 22 d of life of N. rachovii ( 7% of total life), suffering a general RAR impairment mainly reflected by changes in phase regularity, complexity, amplitude and the ability to stay synchronized to the LD cycle. Also, an equation of days remaining of life, based on the RAR description, has been calculated and proposed as a tool to identify close-to-death individuals which could be subjected to an adequate restoring treatment to enhance the CS function and improve their well-being.
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    Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon
    (Taylor and Francis Group, Taylor and Francis, 2012-07-23) Baño-Otalora, Beatriz; Gambini, Juan; Viña, José; Bonet-Costa, Vicent; Reiter, Russel J.; Camello, Pedro Javier; Rol, María Ángeles; Madrid, Juan Antonio; Popovic, Natalija; Popovic Popovic, Miroljub; Anatomía Humana y Psicobiología
    Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was <24 h. Whereas melatonin maintained τ at 24 h for BT and LA in both genotypes, ramelteon treatment had no effect. In the behavioral tests, the number of approaches and time spent exploring novel objects were significantly higher in Tg-CON than WT controls. Brain tissue analysis revealed significant reduction in hippocampal protein oxidation in Tg-MEL and Tg-RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin and ramelteon in this mouse model of AD.
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    Rest-activity circadian rhythms in aged Nothobranchius korthausae. The effects of melatonin
    (Elsevier, 2013-03-04) Lucas-Sánchez, Alejandro; Almaida Pagán, Pedro Francisco; Martínez-Nicolás, Antonio; Madrid, Juan Antonio; Mendiola, Pilar; Costa, Jorge de; Fisiología
    Adult (48-week-old) and senescent (72-week-old) individually-kept Nothobranchius korthausae were used as experimental subjects to characterise circadian system (CS) function and age-related changes in enescent fish. This species was specifically chosen because it has already shown potential for use as a model system in gerontological studies. The rest-activity rhythm (RAR) in fish can be easily monitored and used to characterise the state of the CS, and it has also been proposed as a reliable model to study sleep-like periods in fish. As they aged, N. korthausae experienced a significant decrease in total daily activity and a progressive impairment of the RAR, accompanied by changes in the regularity, fragmentation and amplitude of the rhythm. The ability of the CS to oscillate autonomouslywhen the twomain synchronizers, photoperiod and feeding time,were absent (continuous darkness and randomfeeding), was also impaired with age, as the capacity to re-synchronise to the light–dark (LD) cycle declined. Melatonin treatment improved the regularity, fragmentation and amplitude of the RAR in senescent fish, and it also improved sleep efficiency. In conclusion,N. korthausae represents a viablemodel for studying the aging of the circadian system and the restorative effect of chronobiotic substances, such as melatonin.