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Team prevents memory problems caused by sleep deprivation

December 13, 2014 Leave a comment

The hippocampus of a mouse in the University of Pennsylvania study glows green where cells have taken up a receptor that triggers a cAMP signalling pathway. After administering the ligand to the receptor, researchers could selectively boost cAMP levels in this region and this cell type only. They found that ‘rescuing’ these cells with a shot of cAMP preventing the memory problems that sleep loss can induce. Credit: University of Pennsylvania

Sleep is a critical period for memory consolidation, and most people don’t get enough. Research has shown that even brief periods of sleep deprivation can lead to deficits in memory formation.

In a new study, published in the Journal of Neuroscience, a team led by scientists from the University of Pennsylvania found that a particular set of cells in a small region of the brain are responsible for memory problems after sleep loss. By selectively increasing levels of a signaling molecule in these cells, the researchers prevented mice from having .

Robbert Havekes was the lead author on the study. He is a research associate in the lab of Ted Abel, the study’s senior author and Brush Family Professor of Biology in Penn’s School of Arts & Sciences. Coauthors from the Abel lab included Jennifer C. Tudor and Sarah L. Ferri. They collaborated with Arnd Baumann of Forschungszentrum Jülich, Germany, and Vibeke M. Bruinenberg and Peter Meerlo of the University of Groningen, The Netherlands.

In 2009, a group from Abel’s lab published a study in Nature that identified the cyclic AMP, or cAMP, signaling pathway as playing a role in sleep-loss-associated . Whereas depriving mice of sleep impaired their spatial memory, restoring levels of cAMP in their brain prevented this effect.

“The challenge following this important study,” Abel said, “was to determine if the impact of  was mediated by particular regions of the brain and particular neural circuits. We suspected that the hippocampus, the brain region that mediates spatial navigation and contextual memory, was critical.”

In the current work, they set out to answer these questions. They targeted excitatory neurons because of their importance in transmitting signals in the brain and the fact that their functioning relies on cAMP signaling. The limitation of previous studies was that they lacked a way to increase cAMP in just one area of the brain in a cell-type specific fashion. Havekes, Abel and colleagues devised a way of doing this that they term a “pharmacogenetic” approach, blending genetic modification and drug administration.

They engineered a non-pathogenic virus to harbor the gene encoding the receptor for the protein octopamine, which triggers cAMP pathway activation in fruit flies but is not naturally found in the brains of mice. The researchers injected this virus into the hippocampus of mice so that the excitatory neurons in that region alone would express the octopamine receptor.

“It sounds weird. Why would you put a receptor there that is never going to be activated?” Havekes said. “The trick is, you follow that up by giving mice the ligand of the receptor, which is octopamine, and that will activate the receptors only where they are present.”

The team confirmed that only the excitatory hippocampal neurons expressed the receptor and that they could selectively increase cAMP levels in only these cells by giving the mice a systemic injection of octopamine.

“This way, we could manipulate the cAMP pathways that we previously saw being affected by sleep deprivation but selectively in specific neural circuits in the brain,” Havekes says.

With this pharmacogenetic tool in hand, Havekes, Abel and colleagues began the sleep deprivation tests with the mice expressing the octopamine receptor in their hippocampus. First the researchers trained mice in a spatial memory task. They put them in a box that had three different objects, each in a distinct location.

Then, because previous research had shown that cAMP signaling contributes to hippocampus-dependent  in two time windows—first directly after training and again three to four hours after training—the researchers gave mice in the experimental groups injections of octopamine in both of these windows to boost cAMP levels.

Mice receiving the cAMP boost were divided into two groups: One was left to sleep undisturbed, while the other was sleep-deprived for five hours by gently tapping their cage or rearranging their bedding.

One full day after the initial training, all of the mice were tested again. This time, there was a twist: one of the objects originally in the box had been moved to a new location.

“If the mice had learned and remembered the location of the objects during their training, then they would realize, okay, this is the object that has moved, and they’ll spend more time exploring that particular object,” Havekes explained. “If they didn’t remember well, they would explore all the objects in a random fashion.”

The researchers found that the sleep-deprived mice that received the octopamine injections spent more time exploring the object that had moved, just as mice that had not been sleep deprived did. On the other hand, sleep-deprived  that didn’t express the receptor explored all the objects at random, a sign that they had failed to remember the locations of the objects from their initial training as a result of the brief period of sleep deprivation.

“What we’ve shown is this memory loss due to sleep deprivation is really dependent on misregulation of cAMP signaling in the excitatory neurons of the hippocampus,” Havekes said.

As a next step, the group would like to explore what cAMP is doing to help consolidate memory. They would also like to investigate how other cell types in the brain, such as astrocytes, might be affected. And finally, while this study focused on the impact of a brief period of sleep deprivation, Havekes is curious to know how not getting enough sleep on a daily basis, as is more similar to human experiences, might be affecting .

“Thinking about people who do shift work or doctors who work long hours, if we can tackle the cognitive problems that result from , that would be a great thing,” Havekes said.

“At least in the mouse using these sophisticated tools, we’re able to reverse the negative impact of sleep deprivation on cognition,” Abel said.

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Swine flu vaccine linked to child narcolepsy: EU watchdog

September 30, 2012 Leave a comment

 

A swine flu vaccine used in 2009-10 is linked to a higher risk of the sleeping disorder narcolepsy in children and teens in Sweden and Finland, the European Centre for Disease Prevention and Control said Friday.

The EU agency studied the effects of the Pandemrix vaccine on children in eight European countries after Sweden and Finland reported higher incidences of narcolepsy among children who were inoculated with the vaccine during the swine flu pandemic in 2009 and 2010.

“The case-control study found an association between vaccination with Pandemrix and an increased risk of narcolepsy in children and adolescents (five to 19 years of age) in Sweden and Finland,” the ECDC said.

“The overall number of new cases of narcolepsy being reported after September 2009 was much higher in Sweden and Finland … compared with the other countries participating in the study,” it said.

In the six other countries—Britain, Denmark, France, Italy, The Netherlands and Norway—no link was found based on a strict statistical analysis, which tried to address media bias.

However, other confirmatory analyses did identify an increased risk, the report said.

The report included several recommendations for further study to try to distinguish between true vaccine effects and media attention.

An ECDC spokesman said that while the study did not quantify the increased risk compared with non-vaccination, national studies showed the risk of developing narcolepsy after taking Pandemrix, which is produced by British drug company GlaxoSmithKline, was around one in 20,000 for children and adolescents.

Narcolepsy is a chronic nervous system disorder that causes excessive drowsiness, often causing people to fall asleep uncontrollably, and in more severe cases to suffer hallucinations or paralysing physical collapses called cataplexy.

In Finland, 79 children aged four to 19 developed narcolepsy after receiving the Pandemrix vaccine in 2009 and 2010, while in Sweden the number was close to 200, according to figures in the two countries.

Both countries recommended their populations, of around five and 10 million respectively, to take part in mass vaccinations during the swine flu scare. Pandemrix was the only vaccine used in both countries.

Meanwhile, a recent study in the medical journal The Lancet said that between five and 17 people in Finland aged 0-17 are estimated to have died as a direct result of the 2009-10 swine flu pandemic, while the same number for Sweden was nine to 31.

In the past year, the Finnish and Swedish governments have both agreed to provide financial compensation for the affected children after their own national research showed a link between the inoculation and narcolepsy.

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The above story is reprinted from MedicalXpress.

 

Brain Waves

February 10, 2012 3 comments

Introduction Brain waves

The brain generates tiny electrical pulses as The brain produces four main waves with thoughts traverse the labyrinth of the mind. The specific frequencies:

physical conduits of these thoughts are the millions of nerve cells or neurons in the brain. Just as radio signals, in order to make a comprehensible message, are beamed out on radio waves, a band of signals within a defined frequency, so the brain’s activity also occurs in waves. Brain waves can be measured on an electro-encephalograph machine (which is normally abbreviated to EEG Machine). By attaching sensitive electrodes to the scalp, it is possible to measure accurately the type of brain wave that a subject is producing. These waves are usually expressed in the number of cycles per second (CPS) or with their frequency (Hz).

1. Beta level brain waves – range 12-16 Hz (also 13-25 Hz)

2. Alpha level brain waves – range 8-12 Hz 3. Theta level brain waves – range 4-7 Hz
4. Delta level brain waves – range 0.5-3 Hz

The following chart relates each type of brain wave to its principal function. We must remember however, that when we speak of someone being ‘in alpha’ we mean that this is their characteristic and predominant brain wave. Other brain waves will also be present, but in smaller quantities than usual.

Brain activities

The linking of left and right brain activities is important in producing a shift from learning to accelerated learning. Yet our society is very ‘beta orientated’. We are busy thinking about the problem in hand, but don’t leave ourselves sufficiently open to other influences, which would help us memorize faster and make the sort of less expected connections that we call creative thinking.

Beta brain

In beta you don’t see the wood for concentrating on the trees. But learn to relax, increase the proportion of the alpha and ideally theta brain waves, and you have created the conditions where you may begin to see the whole picture.

Alpha brain

‘Alpha’ is a natural and receptive state of mind, that we can all attain through the techniques of relaxation. They principally involve simple and pleasant relaxation exercises and listening to certain types of music.

Theta brain

The theta brain wave pattern is especially interesting. It occurs spontaneously to most of us in the twilight state between being fully awake and falling asleep. Arthur Koestler called it ‘reverie’. This drowsy stage is associated with fleeting semi-hallucinatory images. Thousands of artistic and literary inspirations and scientific inventions have been credited to this state, a sort of freeform thinking that puts you in touch with your subconscious.

Brain waves interpretation

Many psychologists would agree it is a reasonable hypothesis that, when left/right brain symbiosis takes place, conscious and subconscious are also united. The proportion of theta brain waves becomes much higher than normal. This is the moment when logical left brain activity declines. The left brain, which normally acts as a filter or censor to the subconscious, drops its guard, and allows the more intuitive, emotional and creative depths of the right brain to become increasingly influential.

If the hypothesis is true, then do women, popularly characterised as more intuitive, reach a walking theta state more often than men; and can this be associated with the fact that their left/right brain link, the Corpus callosum, is larger and richer in connective capabilities than men’s? We do not yet know, but it is a fascinating area for future research.

At the University of Colorado Medical Centre and at the Biofeedback Centre in Denver, Dr. Thomas Budzyski has found that, when people were trained to achieve and maintain theta brain waves using biofeedback techniques, they did indeed learn much faster. Moreover, many emotional and attitudinal problems were solved at the same time.

To read more click on this link to the full article: Brain Waves (pdf).