Long-term study supports detrimental effects of television viewing on sleep in young children

A study following more than 1,800 children from ages 6 months to nearly 8 years found a small but consistent association between increased television viewing and shorter sleep duration. The presence of a television in the room where a child sleeps also was associated with less sleep, particularly in minority children. Investigators from MassGeneral Hospital for Children (MGHfC) and Harvard School of Public Health (HSPH) report their results – the first to examine the connection between television and sleep duration over several years – in the May issue of Pediatrics.

The study participants, children and their mothers, were enrolled in Project Viva, a long-term investigation of the health effects of several factors during pregnancy and after birth. This study analyzed information – reported by mothers when the children were around 6 months old and then annually for the next seven years – regarding how much time each day infants were in a room where a television was on, how much time older children watched television daily, whether children ages 4 to 7 slept in a room where a TV was present and their child’s average daily amount of sleep.

The study revealed that, over the course of the study, each additional hour of television viewing was associated with 7 fewer minutes of sleep daily, with the effects appearing to be stronger in boys than in girls. Racial and ethnic minority children were much more likely to sleep in a room where a television was present, and among those children, the presence of a bedroom television reduced average sleep around a half-hour per day.

The study authors note their results support previous short-term studies finding that both television viewing and sleeping in a room with a television decrease total sleep time, which can have negative effects on both mental and physical health.

Dynorphin Acts as a Neuromodulator to Inhibit Itch in the Dorsal Horn of the Spinal Cord

Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5−/− mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.

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Transplanting interneurons: Getting the right mix

Despite early optimistic studies, the promise of curing neurological conditions using transplants remains unfulfilled. While researchers have exhaustively cataloged different types of cells in the brain, and also the largely biochemical issues underlying common diseases, neural repair shops are still a ways off. Fortunately, significant progress is being made towards identifying the broader operant principles that might bear on any one disease work-around. A review just published in Science focuses on recent work on transplanting interneurons—a diverse family of cells united by their mutual love of inhibition and their local loyalty. The UCLA-based authors, reach the conclusion that the fate of transplanted neurons ultimately depends less on the influences of the new host environment, and more on the early upbringing of the cells within the donor embryo.

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(Image caption: Blockade of p25 generation in the brain of an Alzheimer’s disease mouse model mitigates amyloid plaque buildup. Hippocampal slices from a seven-month-old 5XFAD mouse (left) or 5XFAD;p35KI mouse (right), alongside markers for Aβ (red) and activated astrocyte (green). Nuclei are shown in blue.)

Neuroscientists find that limiting a certain protein in the brain reverses Alzheimer’s symptoms in mice

Limiting a certain protein in the brain reverses Alzheimer’s symptoms in mice, report neuroscientists at MIT’s Picower Intitute for Learning and Memory.

Researchers found that the overproduction of the protein known as p25 may be the culprit behind the sticky protein-fragment clusters that build up in the brains of Alzheimer’s patients. The work, which was published in the April 10 issue of Cell, could provide a new drug target for the treatment of the disease that affects more than five million Americans, says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and senior author of the paper.

Abnormal clusters of protein fragments, known as beta amyloid plaques, are believed to cause the cognitive impairments, cell death, and tissue loss associated with Alzheimer’s. The p25 protein had been tied to the creation and buildup of beta amyloids, but until now, p25’s role in Alzheimer’s pathology was not well understood.

“This protein appears to help maintain normal brain activity, but also is part of a feedback loop with beta amyloids. It generates the plaques which, in turn, boost levels of p25,” Tsai says.

Lead author of the paper is Jinsoo Seo, a postdoc associate at the Picower Institute.

The benefits of p25 generation

Elevated p25 levels in the brain have been documented upon exposure to neurotoxic stimuli such as oxidative stress and beta amyloids.

“In this study, for the first time we show that a variety of physiological neuronal activities generate p25 in the hippocampus, where memories are encoded in the brain,” Tsai says.

To delineate the precise roles of p25, Tsai’s lab generated a transgenic mouse model, which enabled researchers to prevent the production of p25 without altering other proteins with essential roles in brain development.

The researchers found that p25 is required for synaptic plasticity, the ability of brain connections to change over time; especially for the process called long-term depression (LTD) that selectively weakens sets of synapses and is associated with memory extinction.

Tsai’s team observed that the mice unable to generate p25 could learn new tasks and form memories normally; however, when the researchers began to address memory extinction, they soon noticed that the mice have difficulties with replacing older memories with newer ones.

Too much of a good thing

“This finding not only boosts our understanding of p25 in synaptic functions, but also explains the underlying mechanism of the inordinate synaptic depression observed in the Alzheimer’s brain,” Seo says.

“This finding led us to question whether the blockade of p25 generation could mitigate pathological phenotypes in the Alzheimer’s brain,” Tsai says.

In the mouse model of Alzheimer’s disease, inhibiting p25 production improved cognitive function, greatly reduced plaque formation and neuroinflammation, hallmark features of Alzheimer’s disease.

These results hold out the hope that a drug that regulates p25 could benefit Alzheimer’s disease patients by improving cognitive function and perhaps delaying the development of brain pathology, Tsai says.

Neuroscientists Find Brain Activity May Mark the Beginning of Memories

By tracking brain activity when an animal stops to look around its environment, neuroscientists at Johns Hopkins University believe they can mark the birth of a memory.

Using lab rats on a circular track, James Knierim, professor of neuroscience in the Zanvyl Krieger Mind/Brain Institute at Johns Hopkins, and a team of brain scientists, noticed that the rats frequently paused to inspect their environment with head movements as they ran. The scientists found that this behavior activated a place cell in their brain, which helps the animal construct a cognitive map, a pattern of activity in the brain that reflects the animal’s internal representation of its environment.

In a paper recently published in the journal Nature Neuroscience, the researchers state that when the rodents passed that same area of the track seconds later, place cells fired again, a neural acknowledgement that the moment has imprinted itself in the brain’s cognitive map in the hippocampus.

The hippocampus is the brain’s warehouse for long- and short-term processing of episodic memories, such as memories of a specific experience like a trip to Maine or a recent dinner. What no one knew was what happens in the hippocampus the moment an experience imprints itself as a memory.

“This is like seeing the brain form memory traces in real time,” said Knierim, senior author of the research. “Seeing for the first time the brain creating a spatial firing field tied to a specific behavioral experience suggests that the map can be updated rapidly and robustly to lay down a memory of that experience.”

A place cell is a type of neuron within the hippocampus that becomes active when an animal or human enters a particular place in its environment. The activation of the cells help create a spatial framework much like a map, that allows humans and animals to know where they are in any given location. Place cells can also act like neural flags that “mark” an experience on the map, like a pin that you drop on Google maps to mark the location of a restaurant.

“We believe that the spatial coordinates of the map are delivered to the hippocampus by one brain pathway, and the information about the things that populate the map, like the restaurant, are delivered by a separate pathway,” said Knierim. “When you experience a new item in the environment, the hippocampus combines these inputs to create a new spatial marker of that experience.”

In the experiments, researchers placed tiny wires in the brains of the rats to monitor when and where brain activity increased as they moved along the track in search of chocolate rewards. About every seven seconds, the rats stopped moving forward and turned their heads to the perimeter of the room as they investigated the different landmarks, a behavior called “head-scanning.”

“We found that many cells that were previously silent would suddenly start firing during a specific head-scanning event,” said Knierim. “On the very next lap around the track, many of these cells had a brand new place field at that exact same location and this place field remained usually for the rest of the laps. We believe that this new place field marks the site of the head scan and allows the brain to form a memory of what it was that the rat experienced during the head scan.”

Knierim said the formation and stability of place fields and the newly-activated place cells requires further study. The research is primarily intended to understand how memories are formed and retrieved under normal circumstances, but it could be applicable to learning more about people with brain trauma or hippocampal damage due to aging or Alzheimer’s.

“There are strong indications that humans and rats share the same spatial mapping functions of the hippocampus, and that these maps are intimately related to how we organize and store our memories of prior life events,” said Knierim. “Since the hippocampus and surrounding brain areas are the first parts of the brain affected in Alzheimer’s, we think that these studies may lend some insight into the severe memory loss that characterizes the early stages of this disease.”

(Image: Shutterstock)

New finding suggests a way to block stress’ damage

Ketamine, an anesthetic sometimes abused as a street drug, increases the synaptic connections between brain cells and in low doses acts as a powerful antidepressant, Yale researchers have found. However, stress has the opposite effect, shrinking the number of synaptic spines, triggering depression.

In the April 13 online issue of the journal Nature Medicine, Yale researchers found that expression of single gene called REDD1 enables stress to damage brain cells and cause depressive behavior.

“We found if we delete REDD1, we can block the effects of stress in mice,” said Ron Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and professor of neurobiology.

In recent studies, the Yale team showed that ketamine activates the mTORC1 pathway, which in turn spurs synthesis of synaptic proteins and connections. In the new study, they show that the REDD1 gene expression blocks mTORC1 activity and decreases the number of synaptic connections. The new study by Duman and lead author Kristie Ota showed that mice without the REDD1 gene were impervious to the synaptic and behavioral deficits caused by stress. By contrast, when the gene was over-expressed, mice exhibited loss of synaptic connections and increased depression and anxiety behaviors.

In addition, post-mortem examinations of people who had suffered from depression showed high levels of REDD1 in cortical regions associated with depression.

Yale’s work with ketamine has already led to development of new classes of antidepressants, which are currently in clinical trials. Duman said these new findings may provide a new drug target that directly blunts the negative impacts of stress.

Study says we’re over the hill at 24

It’s a hard pill to swallow, but if you’re over 24 years of age you’ve already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

SFU’s Joe Thompson, a psychology doctoral student, associate professor Mark Blair, Thompson’s thesis supervisor, and Andrew Henrey, a statistics and actuarial science doctoral student, deliver the news in a just-published PLOS ONE Journal paper.

In one of the first social science experiments to rest on big data, the trio investigates when we start to experience an age-related decline in our cognitive motor skills and how we compensate for that.

The researchers analyzed the digital performance records of 3,305 StarCraft 2 players, aged 16 to 44. StarCraft 2 is a ruthless competitive intergalactic computer war game that players often undertake to win serious money.

Their performance records, which can be readily replayed, constitute big data because they represent thousands of hours worth of strategic real-time cognitive-based moves performed at varied skill levels.

Using complex statistical modeling, the researchers distilled meaning from this colossal compilation of information about how players responded to their opponents and more importantly, how long they took to react.

“After around 24 years of age, players show slowing in a measure of cognitive speed that is known to be important for performance,” explains Thompson, the lead author of the study, which is his thesis. “This cognitive performance decline is present even at higher levels of skill.”

But there’s a silver lining in this earlier-than-expected slippery slope into old age. “Our research tells a new story about human development,” says Thompson.

“Older players, though slower, seem to compensate by employing simpler strategies and using the game’s interface more efficiently than younger players, enabling them to retain their skill, despite cognitive motor-speed loss.”

For example, older players more readily use short cut and sophisticated command keys to compensate for declining speed in executing real time decisions.

 The findings, says Thompson, suggest “that our cognitive-motor capacities are not stable across our adulthood, but are constantly in flux, and that our day-to-day performance is a result of the constant interplay between change and adaptation.”

Thompson says this study doesn’t inform us about how our increasingly distracting computerized world may ultimately affect our use of adaptive behaviours to compensate for declining cognitive motor skills.

But he does say our increasingly digitized world is providing a growing wealth of big data that will be a goldmine for future social science studies such as this one.

A single switch dictates severity of epileptic seizures

A switch in the brain of people with epilepsy dictates whether their seizures will be relatively mild or lead to a dangerous and debilitating loss of consciousness, Yale researchers have found.

The study published April 11 in the journal Neurology showed that there was no gradation of impairment during seizures — subjects were either alert or totally unaware of their surroundings.

The existence of an “all or none” switch for consciousness surprised researchers, who expected to find different levels of awareness among those who experience focal seizures, or those localized to particular brain areas.

“During seizures patients may report a funny, fearful feeling, tingling in their arm or some quirk in their vision but are able to answer all our questions,” said Dr. Hal Blumenfeld, professor of neurology, neurobiology, and neurosurgery, and senior author of the study. “At other times — boom — all of a sudden they are in a daze, unable to respond to their environment.”

Blumenfeld said previous studies have shown that this switch rests in areas of the brain stem that play a role in waking and in paying attention to your surroundings. The findings suggest that existing drugs that treat narcolepsy or therapies like deep brain stimulation might help patients with intractable epilepsy.

“Our goal is to prevent seizures, but in a fifth to a quarter of people have seizures no matter what we do,” Blumenfeld said. “For them, therapies that would prevent loss of consciousness would greatly improve quality of life.”

Team Solves Decades-Old Mystery of How Cells Keep from Bursting

A team led by scientists at The Scripps Research Institute (TSRI) has identified a long-sought protein that facilitates one of the most basic functions of cells: regulating their volume to keep from swelling excessively.

The identification of the protein, dubbed SWELL1, solves a decades-long mystery of cell biology and points to further discoveries about its roles in health and disease—including a serious immune deficiency that appears to result from its improper function.

“Knowing the identity of this protein and its gene opens up a broad new avenue of research,” said the study’s principal investigator Ardem Patapoutian, a Howard Hughes Medical Institute (HHMI) Investigator and professor at TSRI’s Dorris Neuroscience Center and Department of Molecular and Cellular Neuroscience.

The report appears as the cover story in the April 10, 2014 issue of the journal Cell.

Unraveling the Mystery

Water passes through the membrane of most cells with relative ease and tends to flow in a direction that evens out the concentration of dissolved molecules or “solutes.” “Water in effect follows the solutes,” explained Zhaozhu Qiu, a member of the Patapoutian laboratory who was first author of the study. “Any decrease in the solute concentration outside a cell or an increase within the cell will make the cell swell with water.”

For decades, experiments have demonstrated the existence of a key relief valve for this swelling: an unidentified ion channel in the cell membrane, dubbed VRAC (volume-regulated anion channel). VRAC opens in response to cell swelling and permits an outflow of chloride ions and some other negatively charged molecules—which water molecules follow, thus reducing the swelling.

“For the past 30 years, scientists have known that there is this VRAC channel, and yet they haven’t known its molecular identity,” said Patapoutian.

Finding the proteins that make VRAC and their genes was a goal that had eluded prior attempts because of the technical hurdles involved. However, in the new study, Qiu and his colleagues were able to set up a rapid, “high-throughput” screening test based on fluorescence. They engineered human cells to produce a fluorescent protein whose glow would be quenched when the cells became swollen and VRAC channels opened.

With the help of automated screening specialists at the La Jolla-based Genomics Institute of the Novartis Research Foundation (GNF), which recently began a broad new collaboration agreement with TSRI, the team cultured large arrays of the cells and, using a technique known as RNA interference, blocked the activity of a different gene for each clump of cells.

The idea was to watch for the groups of cells that continued to glow—indicating that the gene inactivation had disrupted VRAC.

In this way, with several rounds of tests, the team sifted through the human genome and ultimately found one gene whose disruption reliably terminated VRAC activity. It was a gene that had been discovered in 2003 and catalogued as “LRRC8.” Although it appeared to code for a cell-membrane-spanning protein—as one would expect for an ion channel—almost nothing else was known about it.

The team renamed it SWELL1.

Potential Roles in Disease

Investigating further, the researchers showed that SWELL1 does indeed localize to the cell membrane as an ion channel protein would. Experiments by Adrienne Dubin, a staff scientist at TSRI, showed that certain mutations of SWELL1 alter the VRAC channel’s ion-passing properties—indicating that SWELL1 is a central feature of the ion channel itself.

“It is at least a major part of the VRAC channel for which cell biologists have been searching all this time,” said Patapoutian.

Patapoutian, Qiu and their colleagues now will study SWELL1 further, including an examination of what happens to lab mice that lack the protein in various cell types.

Curiously, the gene for SWELL1 was first noted by scientists because a mutant, dysfunctional form of it causes a very rare type of agammaglobulinemia—a lack of antibody-producing B cells, which leaves a person unusually vulnerable to infections. That suggests that SWELL1 is somehow required for normal B-cell development.

“There also have been suggestions from prior studies that this volume-sensitive ion channel is involved in stroke because of the brain-tissue swelling associated with stroke and that it may be involved as well in the secretion of insulin by pancreatic cells,” said Patapoutian. “So there are lots of hints out there about its relevance to disease—we just have to go and figure it all out now.”