77 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
Parental obesity and risk factors for cardiovascular disease among their offspring in mid-life: findings from the 1958 British Birth Cohort Study
Background:Few studies have investigated whether parental adiposity is associated with offspring cardiovascular health or the underlying pathways. Studying these associations may help to illuminate the paradox of increasing prevalence of obesity and declining trends in cardiovascular disease (CVD) mortality, which may be partially explained by beneficial adaptations to an obesogenic environment among people exposed to such environments from younger ages.Objective:To investigate associations between parental body mass index (BMI) and risk factors for CVD among their offspring in mid-life and to test whether associations of offspring BMI with CVD risk factors were modified by parental BMI.Methods:Data from parents and offspring in the 1958 British birth cohort were used (N=9328). Parental BMI was assessed when offspring were aged 11 years; offspring BMI, waist circumference and CVD risk factors (lipid levels, blood pressure, glycosylated haemoglobin (HbA1c) and inflammatory and haemostatic markers) were measured at 44-45 years.Results:Higher parental BMI was associated with less favourable levels of offspring risk factors for CVD. Most associations were maintained after adjustment for offspring lifestyle and socioeconomic factors but were largely abolished or reversed after adjustment for offspring adiposity. For some CVD risk factors, there was evidence of effect modification; the association between higher BMI and an adverse lipid profile among offspring was weaker if maternal BMI had been higher. Conversely, offspring BMI was more strongly associated with HbA1c if parental BMI had been higher.Conclusions:Intergenerational influences may be important in conferring the effect of high BMI on CVD risk among offspring
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
Sleep-wake regulation is altered in leptin-resistant (db/db) genetically obese and diabetic mice
Recent epidemiological and clinical studies indicate that the control of sleep-wake states may be an important factor in the regulation of energy metabolism. Leptin is a peripherally synthesized hormone that has critical signaling properties in the brain for the control of long-term energy homeostasis. In this study, we examined the hypothesis that leptin signaling exerts a role in sleep-wake regulation and that leptin may represent an important mechanistic link in the coordination of sleep-wake states and metabolism. Sleep-wake patterns were recorded in a genetic mouse model of obesity and diabetes, the db/db mouse, which harbors a mutation in a particular isoform of the leptin receptor (long form, LRb). We found that db/db mice exhibit a variety of alterations in sleep regulation, including an increase in overall sleep time, a dramatic increase in sleep fragmentation, attenuated diurnal rhythmicity in rapid eye movement sleep and non-rapid eye movement EEG delta power (a measure of sleep homeostatic drive), and a decrease in the compensatory response to acute (i.e., 6 h) sleep deprivation. The db/db mice also generated low amounts of locomotor activity and a reduction in the diurnal rhythm of activity. These results indicate that impaired leptin signaling has deleterious effects on the regulation of sleep amount, sleep architecture, and temporal consolidation of these arousal states. In summary, leptin may represent an important molecular component in the integration of sleep, circadian rhythms, and energy metabolism
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