Scientists provide first evidence that carbamates can upset circadian rhythms

 The current research focuses on two chemicals, carbaryl, the third most widely used insecticide in the U.S. but which is illegal in several countries, and carbofuran, the most toxic carbamate insecticide, which has been banned for applications on food crops for human consumption since 2009. It is still used in many countries, including Mexico and traces persist in food, plants and wildlife.
"We found that both insecticides are structurally similar to melatonin and that both showed affinity for the melatonin, MT2 receptors, that can potentially affect glucose homeostasis and insulin secretion," said Marina Popovska-Gorevski, co-author, now a scientist with Boehringer Ingelheim Pharmaceuticals, who worked in Dubocovich's lab while earning her master's degree at UB. "That means that exposure to them could put people at higher risk for diabetes and also affect sleeping patterns.""

Gut Microbes Influence Circadian Clock | The Scientist Magazine®

The mammalian gut microbiome is involved in controlling the circadian
rhythm of its host, according to a mouse study published today (April
16) in Cell Host & Microbe. In both mice and humans, timing of feeding and diet type can impact the bacterial populations of the gut. Now, Eugene Chang
of the University of Chicago Medical Center and his colleagues have
found that mouse gut microbiota produce metabolites in diurnal patterns,
and these can influence the expression of circadian clock genes in the
liver.
The results provide additional support for the idea that the gut microbiome is dynamic, said Satchidananda Panda
of the Salk Institute for Biological Studies who was not involved in
the work. “At night, we go to bed with a bunch of bugs in our stomachs
and wake up in the morning with a different set of bugs,” said Panda.
“The implications are pretty big because there are more bacterial cells
in our guts than the number of cells in our body and these species
produce different enzymes and factors that have a big impact on our
overall metabolism.”

JCI - 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.

How body clock affects inflammation: Discovery could accelerate body's response to infection, autoimmune disorders

 "The study published in the Nov. 8 edition of Science identifies a previously hidden pathway by which the body's circadian clock controls the numbers of key inflammatory cells called interleukin-17-producing CD4+ T helper cells (TH17). The work could lead to new ways to rev up the body's immune response to infection or dampen that response in the case of autoimmune diseases in which the body attacks its own tissues, said senior author Dr. Lora Hooper, Professor of Immunology and Microbiology and a Howard Hughes Medical Institute (HHMI) Investigator."

Circadian patterns of gene expression in the human brain and disruption in major depressive disorder

A cardinal symptom of major depressive disorder (MDD) is the disruption of circadian patterns. However, to date, there is no direct evidence of circadian clock dysregulation in the brains of patients who have MDD. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain were difficult to characterize. Here, we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-h cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses (“controls”) and 34 patients with MDD. Our dataset covered ∼12,000 transcripts in the dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, nucleus accumbens, and cerebellum. Several hundred transcripts in each region showed 24-h cyclic patterns in controls, and >100 transcripts exhibited consistent rhythmicity and phase synchrony across regions. Among the top-ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERBa), DBP, BHLHE40 (DEC1), andBHLHE41(DEC2). The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in the brains of patients with MDD due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This transcriptome-wide analysis of the human brain demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggests potentially important molecular targets for treatment of mood disorders.

Luminous Bacteria Control Clock Genes In Host's Body

MNY: Another new study takes a further step toward revealing the pervasive influence microbial communities that inhabit plants and animals have on their biology. Scientists in the US have discovered that the luminous bacterium Vibrio fischeri regulates the daily rhythm of its host, the Hawaiian bobtail squid, by interacting with its clock genes. "

Our internal clocks can become ticking time bombs for diabetes and obesity

"If you're pulling and all-nighter to finish a term paper, a new parent up all night with a fussy baby, or simply can't sleep like you once could, then you may be snoozing on good health. That's because new research published in The FASEB Journal used mice to show that proper sleep patterns are critical for healthy metabolic function, and even mild impairment in our circadian rhythms can lead to serious health consequences, including diabetes and obesity."


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Futurity.org – Why bodies store fat when we eat at night

Insulin activity is controlled by the body’s circadian clock, which helps explain why not only what you eat, but when you eat, matters.

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Aberrant light directly impairs mood and learning through melanopsin-expressing neurons : Nature : Nature Publishing Group

The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep–wake cycles to the correct temporal niche. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.

GEN | News Highlights:Gene Predicts Time of Death

A common variant in the perion gene PER1 separates early birds from night owls, and can even predict someone’s hour of death.

The findings—published in the November issue of the journal Annals of Neurology—could help people schedule anything from work to medical treatments, while offering clues to the conditions of vulnerable patients.

Bright light At Night Can Cause Depression

"Basically, what we found is that chronic exposure to bright light - even the kind of light you experience in your own living room at home or in the workplace at night if you are a shift worker - elevates levels of a certain stress hormone in the body, which results in depression and lowers cognitive function."

It's not just what you eat, but when you eat it

Fat cells store excess energy and signal these levels to the brain. In a new study this week in Nature Medicine, Georgios Paschos PhD, a research associate in the lab of Garret FitzGerald, MD, FRS director of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, shows that deletion of the clock gene Arntl, also known as Bmal1, in fat cells, causes mice to become obese, with a shift in the timing of when this nocturnal species normally eats. These findings shed light on the complex causes of obesity in humans.

Read more at: http://medicalxpress.com/news/2012-11-it-not-just-what-you.html#jCp

Type 2 Diabetes Risk Tied To Short Sleep In Teens

A study of teenagers in the US found that the less sleep they got, the higher the chance of them having insulin resistance, a metabolic condition that increases a person's risk of developing type 2 diabetes.

Human blood metabolite timetable indicates internal body time: PNAS

A convenient way to estimate internal body time (BT) is essential for chronotherapy and time-restricted feeding, both of which use body-time information to maximize potency and minimize toxicity during drug administration and feeding, respectively. Previously, we proposed a molecular timetable based on circadian-oscillating substances in multiple mouse organs or blood to estimate internal body time from samples taken at only a few time points. Here we applied this molecular-timetable concept to estimate and evaluate internal body time in humans. We constructed a 1.5-d reference timetable of oscillating metabolites in human blood samples with 2-h sampling frequency while simultaneously controlling for the confounding effects of activity level, light, temperature, sleep, and food intake. By using this metabolite timetable as a reference, we accurately determined internal body time within 3 h from just two anti-phase blood samples. Our minimally invasive, molecular-timetable method with human blood enables highly optimized and personalized medicine.

Methylphenidate Modifies the Motion of the Circadian Clock

People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light–dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light–dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.

Organized High Fat Diet Changes Metabolism And Prevents Obesity

Recent research suggests a planned high-fat diet can reduce body weight and spark a unique metabolism where ingested fats are stored and used for energy when food is not available.

Eat your fat at the right time to prevent weight gain.

Sleep-wake cycles affect how well our bodies fight disease. The Scientist

People often feel tired when they get sick, and researchers think that the cytokines helping fight infection may induce sleepiness. If immune-system activation can affect sleep, might the converse be true—do sleep cycles affect the immune system? Erol Fikrig and colleagues at the Yale University School of Medicine isolated some of the molecular players in both the circadian and the innate immune systems. They showed that the strength of some immune responses was indeed affected by the time of day.

Researchers discover molecular link between circadian clock disturbances and inflammatory diseases

Scientists have known for some time that throwing off the body's circadian rhythm can negatively affect body chemistry. In fact, workers whose sleep-wake cycles are disrupted by night shifts are more susceptible to chronic inflammatory diseases such as diabetes, obesity and cancer.

Nature: Peroxiredoxins are conserved markers of circadian rhythms : Nature : Nature Publishing Group

Cellular life emerged ~3.7 billion years ago. With scant exception, terrestrial organisms have evolved under predictable daily cycles owing to the Earth’s rotation. The advantage conferred on organisms that anticipate such environmental cycles has driven the evolution of endogenous circadian rhythms that tune internal physiology to external conditions. The molecular phylogeny of mechanisms driving these rhythms has been difficult to dissect because identified clock genes and proteins are not conserved across the domains of life: Bacteria, Archaea and Eukaryota. Here we show that oxidation–reduction cycles of peroxiredoxin proteins constitute a universal marker for circadian rhythms in all domains of life, by characterizing their oscillations in a variety of model organisms. Furthermore, we explore the interconnectivity between these metabolic cycles and transcription–translation feedback loops of the clockwork in each system. Our results suggest an intimate co-evolution of cellular timekeeping with redox homeostatic mechanisms after the Great Oxidation Event ~2.5 billion years ago.

Too little sleep, disrupted internal clock means higher risk of diabetes and obesity

A study by researchers at Brigham and Women's Hospital (BWH) reinforces the finding that too little sleep or sleep patterns that are inconsistent with our body's "internal biological clock" may lead to increased risk of diabetes and obesity. This finding has been seen in short-term lab studies and when observing human subjects via epidemiological studies. However, unlike epidemiological studies, this new study provides support by examining humans in a controlled lab environment over a prolonged period, and altering the timing of sleep, mimicking shift work or recurrent jet lag.