35 research outputs found
Oscillons: an encounter with dynamical chaos in 1953?
We present evidences that Ben F. Laposky (1914-2000) might have been the
first person who created a family of nonlinear analog circuits that allowed him
to observe chaotic attractors and other trademarks of nonlinear science as
early as 1953.Comment: accepted to Chao
Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration
Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator–like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration
Body weight, metabolism and clock genes
Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus) and peripheral (located in other tissues) circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity
Seasonal Changes in Mood and Behavior Are Linked to Metabolic Syndrome
BACKGROUND: Obesity is a major public health problem worldwide. Metabolic syndrome is a risk factor to the cardiovascular diseases. It has been reported that disruptions of the circadian clockwork are associated with and may predispose to metabolic syndrome. METHODOLOGY AND PRINCIPAL FINDINGS: 8028 individuals attended a nationwide health examination survey in Finland. Data were collected with a face-to-face interview at home and during an individual health status examination. The waist circumference, height, weight and blood pressure were measured and samples were taken for laboratory tests. Participants were assessed using the ATP-III criteria for metabolic syndrome and with the Seasonal Pattern Assessment Questionnaire for their seasonal changes in mood and behavior. Seasonal changes in weight in particular were a risk factor of metabolic syndrome, after controlling for a number of known risk and potential confounding factors. CONCLUSIONS AND SIGNIFICANCE: Metabolic syndrome is associated with high global scores on the seasonal changes in mood and behavior, and with those in weight in particular. Assessment of these changes may serve as a useful indicator of metabolic syndrome, because of easy assessment. Abnormalities in the circadian clockwork which links seasonal fluctuations to metabolic cycles may predispose to seasonal changes in weight and to metabolic syndrome
Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms
Background: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic
properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocininduced
diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative
activities in mice in order to examine possible underlying mechanisms.
Methods: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate
and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot
plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The
antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for
prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain
using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia.
Results: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide),
palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the
abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole
reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case
test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was
observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME
decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized
by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative
activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static
and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal
latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency.
Conclusions: These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The
antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and
GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed
Repeated sleep restriction in rats leads to homeostatic and allostatic responses during recovery sleep
Recent studies indicate that chronic sleep restriction can have negative consequences for brain function and peripheral physiology and can contribute to the allostatic load throughout the body. Interestingly, few studies have examined how the sleep–wake system itself responds to repeated sleep restriction. In this study, rats were subjected to a sleep-restriction protocol consisting of 20 h of sleep deprivation (SD) followed by a 4-h sleep opportunity each day for 5 consecutive days. In response to the first 20-h SD block on day 1, animals responded during the 4-h sleep opportunity with enhanced sleep intensity [i.e., nonrapid eye movement (NREM) delta power] and increased rapid eye movement sleep time compared with baseline. This sleep pattern is indicative of a homeostatic response to acute sleep loss. Remarkably, after the 20-h SD blocks on days 2–5, animals failed to exhibit a compensatory NREM delta power response during the 4-h sleep opportunities and failed to increase NREM and rapid eye movement sleep times, despite accumulating a sleep debt each consecutive day. After losing ≈35 h of sleep over 5 days of sleep restriction, animals regained virtually none of their lost sleep, even during a full 3-day recovery period. These data demonstrate that the compensatory/homeostatic sleep response to acute SD does not generalize to conditions of chronic partial sleep loss. We propose that the change in sleep–wake regulation in the context of repeated sleep restriction reflects an allostatic process, and that the allostatic load produced by SD has direct effects on the sleep–wake regulatory system