Model of Anorexia Created Using Stem Cells

Though often viewed as a non-biological disorder, new research suggests 50 to 75 percent of risk for AN may be heritable; with predisposition driven primarily by genetics and not, as sometimes presumed, by vanity, poor parenting or factors related to specific groups of individuals. NeuroscienceNews.com image is for illustrative purposes only.

Findings suggest a strong genetic factor could predispose people to anorexia and other eating disorders. Technique suggests novel gene may contribute to eating disorder.

An international research team, led by scientists at University of California San Diego School of Medicine, has created the first cellular model of anorexia nervosa (AN), reprogramming induced pluripotent stem cells (iPSCs) derived from adolescent females with the eating disorder.

Writing in the March 14th issue of Translational Psychiatry, the scientists said the resulting AN neurons — the disease in a dish — revealed a novel gene that appears to contribute to AN pathophysiology, buttressing the idea that AN has a strong genetic factor. The proof-of-concept approach, they said, provides a new tool to investigate the elusive and largely unknown molecular and cellular mechanisms underlying the disease.

“Anorexia is a very complicated, multifactorial neurodevelopmental disorder,” said Alysson Muotri, PhD, professor in the UC San Diego School of Medicine departments of Pediatrics and Cellular and Molecular Medicine, director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine. “It has proved to be a very difficult disease to study, let alone treat. We don’t actually have good experimental models for eating disorders. In fact, there are no treatments to reverse AN symptoms.”



Primarily affecting young female adolescents between ages 15 and 19, AN is characterized by distorted body image and self-imposed food restriction to the point of emaciation or death. It has the highest mortality rate among psychiatric conditions. For females between 15 and 24 years old who suffer from AN, the mortality rate associated with the illness is 12 times higher than the death rate of all other causes of death.

Though often viewed as a non-biological disorder, new research suggests 50 to 75 percent of risk for AN may be heritable; with predisposition driven primarily by genetics and not, as sometimes presumed, by vanity, poor parenting or factors related to specific groups of individuals.

But little is actually known about the molecular, cellular or genetic elements or genesis of AN. In their study, Muotri and colleagues at UC San Diego and in Brazil, Australia and Thailand, took skin cells from four females with AN and four healthy controls, generated iPSCs (stem cells with the ability to become many types of cells) from these cells and induce these iPSCs to become neurons.



(Previously, Muotri and colleagues had created stem cell-derived neuronal models of autism and Williams syndrome, a rare genetic neurological condition.)

Then they performed unbiased comprehensive whole transcriptome and pathway analyses to determine not just which genes were being expressed or activated in AN neurons, but which genes or transcripts (bits of RNA used in cellular messaging) might be associated with causing or advancing the disease process.

No predicted differences in neurotransmitter levels were observed, the researchers said, but they did note disruption in the Tachykinin receptor 1 (TACR1) gene. Tachykinins are neuropeptides or proteins expressed throughout the nervous and immune systems, where they participate in many cellular and physiological processes and have been linked to multiple diseases, including chronic inflammation, cancer, infection and affective and addictive disorders.

The scientists posit that disruption of the tachykinin system may contribute to AN before other phenotypes or observed characteristics become obvious, but said further studies employing larger patient cohorts are necessary.



“But more to the point, this work helps make that possible,” said Muotri. “It’s a novel technological advance in the field of eating disorders, which impacts millions of people. These findings transform our ability to study how genetic variations alter brain molecular pathways and cellular networks to change risk of AN — and perhaps our ability to create new therapies.”
Source: NEUROSCIENCE NEWS

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When Sport Psychology and Neuroscience meet

By: Jaime F. Adriazola
American Graduate University, Washington DC

A sport company is using the “Neuropriming” (term created it by the company) to stimulate the brain’s motor cortex, and in short is designed to improve sports performance. Neuropriming is related to the ‘transcranial direct-current stimulation’ (tDCS) – which in simple terms is using a small electric current via electrodes on the scalp to stimulate specific areas in the brain.

tDCS brain hacking has for a long time been the territory of clinical labs or DIY hardcore biohackers who share their experience and learn from each other – there is even a sub-red it on the topic. Halo Neuroscience has done its own clinical research, and brought a product to market, and opened the technology to the mainstream in a safe and consistent way.



For three years, Halo Sport ™, headphones were provided only to pro and college teams, Olympic contenders and the military. Now, the company has ramped up production, and the super-high-end headphones are ready for public consumption.

The headphones shoot electrical impulses stimulating the brains motor cortex which in turn increases neuroplasticity creating more synchronous connections between neurons and muscles -and thus allegedly improve athletic performance.

In the context of the temporal lobes, this technique makes perfect sense, since the temporal lobes are involved in processing special sounds and memory. Certain types of sounds may activate the temporal lobes and help them process information more efficiently. It’s likely that certain types of “waves sounds” open new pathways into the mind.

"We're up to the challenge of bringing this to the masses," Chao, co-founder of Halo Sport, said at the company's San Francisco headquarters. "Sports science has definitely come a long way."



The US Olympic ski team uses Halo, as do a slew of MLB, NFL and NBA teams. The 2015 NBA champion Golden State Warriors spent this past record-breaking season piloting the headphones. Other world-class athletes, like US Olympic track star Mike Rodgers, swear by them.
In Halo’s own words: “accelerates the optimization of neuromuscular circuitry through training. Improved neuromuscular output leads to more precise, coordinated, and/or explosive movement — whichever the athlete targets during training.”

Nick Davis, a senior lecturer in psychology at Manchester Metropolitan University who has extensively studied tDCS says, “For reasons we don’t really understand, brain cells that are near the positive electrode become a bit more active, and when a brain area is more active, it tends to be more plastic. This is called neuroplasticity, and it relates to the ability to learn things; there is evidence that simple motor actions are learned more readily when they’re done with positive stimulation.”

The directions state to wear the headset and complete a 20 minute neuropriming session before you complete the most intense part of your physical work out, and Halo Sport does not need to be worn during your actual workout. Setting up the primers (the grey electrodes) ready for the priming session can be tricky. They don’t play nice with long hair, and even with short hair can be challenging to get sufficient conductivity to start the session.



Halo Neuroscience claims you will fell a “light tingle” on your head due to the electric current, in reality this felt like more of a sting than a “light tingle” – but it wasn’t unbearable.

The easiest quantifiable improvement was for most exercises, and the less quantifiable results were increased endurance during the first 20 minutes of each workout and increased calories burnt/higher maintained heart rate throughout the sessions (when comparing to similar workouts).

The real energy and improvements seemed to last for about 20 minutes and then seemed to taper off, which means that you should push very hard for the first 20 minutes and then in the last 20 minutes your energy would drop off significantly. It’s not sure if was due to the neuropriming benefits wearing off, or due to pushing yourself too hard due to the benefits in the first 20 minutes and causing you to fatigue. Information has been provided indicating that ‘neuropriming’ was used by the Germany soccer team, during the last World cup.



tDCS (aka. neuropriming) has been shown in clinical settings to improve memory, learning, and intelligence. So I imagine Halo Neuroscience will release products targeted towards different applications in future, and we could actually see a similar device used to improve memory, learning, and intelligence!

Finally we have to mention that tDCS may work more efficiently in combination with ‘Guided Neuro-Psychotherapy”, a new form of therapy that may help athletes increase their potential, and as Doctor Thomas Verny mentioned, “soothing sounds can positively stimulate the brain, and toning balances brain waves, deepens the breath, reduce heart rate, imparts a general sense of well-being, and increase motivation.”

Sources: Halo Neuroscience, Dr. Thomas Verny, Dr. Daniel G. Amen (AMEN clinics, NY), and Dr. Don Campell.

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Breakthrough in the production of dopamine neurons for Parkinson’s

New studies may help to explain the path from stem cells to dopamine neurons.

The Lund experiments use modern global gene expression studies to better understand the path from a stem cell to a dopamine neuron. NeuroscienceNews.com image is credited to university at Buffalo.

The first transplantation of stem cells in patients with Parkinson’s disease is almost within reach. However, it remains a challenge for researchers to control stem cells accurately in the lab in order to achieve successful and functional stem cell therapies for patients.

“Dopamine is an organic chemical of the catecholamine and phenethylamine families that plays several important roles in the brain and body. It is an amine synthesized by removing a carboxyl from a molecule of its precursor chemical L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most multicellular animals.”



“In our preclinical assessments of stem cell-derived dopamine neurons we noticed that the outcome in animal models varied dramatically, even though the cells were very similar at the time of transplantation. This has been frustrating and puzzling, and has significantly delayed the establishment of clinical cell production protocols,” says Malin Parmar who led the study conducted at Lund University as part of the EU network Neuro-Stem-cell-Repair.

The Lund experiments use modern global gene expression studies to better understand the path from a stem cell to a dopamine neuron. The data has been generated in close collaboration with a team of scientists at Karolinska Institute lead by Professor Thomas Perlmann, and is closely linked with a second study from the same cluster of scientists. The second study sheds new light on how dopamine neurons are formed during development, and what makes them different from other similar and neigh boring neurons.

This new insight has enabled a streamlined differentiation process resulting in pure populations of dopamine neurons of high quality.



“We have identified a specific set of markers that correlate with high dopaminergic yield and graft function after transplantation in animal models of Parkinson’s disease. Guided by this information, we have developed a better, and more accurate methods for producing dopamine cells for clinical use in a reproducible way,” says first author Agnete Kirkeby.

The new results, published in two back-to-back articles in the leading journal in the field, Cell Stem Cell, propel stem cell therapy for Parkinson’s disease towards clinical application. The first transplants are expected to be only a few years away.Source: Lund University.

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Breakthrough in Neuroscience: Stimulating Neurons Could Protect Against Brain Damage

Researchers have discovered a previously unknown mechanism that allows neural networks to protect against the spread of secondary brain damage as seen in TBI and ischemic stroke.

A breakthrough in understanding how brain damage spreads – and how it could potentially be limited – has been made through collaboration between neuroscientists and engineers at the Universities of Dundee and Strathclyde.

They have uncovered a previously unknown mechanism in the brain that allows networks of neurons to protect against the kind of spreading secondary damage seen in cases of strokes and traumatic brain injuries.

“If this network activity could be triggered clinically as soon as possible then major brain damage could be minimized and recovery periods shortened,” said Doctor Christopher Connolly, Reader in Neurobiology in the University of Dundee’s School of Medicine.



“Although this is basic laboratory research, it does now re-open the door to the possibility of stopping ongoing brain damage.

“Slow acting neuroprotection is well known but approaches to induce protection require at least 24 hours’ notice to be effective. This is of no practical use in a clinical emergency situation such as a stroke or traumatic brain injury, so current treatment options are limited to aiding the recovery processes.

“We have identified that neuronal networks react to an insult by sending rapid – in minutes – warning signals in an attempt to protect against the toxicity that causes brain damage. If that could be recruited clinically then it would give us a tool to deploy quickly in cases where brain damage was a risk.

“Where we can’t protect neurons quickly, we can recruit the help of surrounding neurons to do this for us. It is a case of `If you need a job done quickly, ask the expert’ and in this instance the experts are the neurons themselves.”



Laboratory-based modelling also showed that the rapid use of benzodiazepines (Valium) appeared to mimic the protection offered by the neuron networks.

“This is something we certainly need to test further but it does suggest the possibility of an effective and immediate pharmacological treatment for stroke,” said Doctor Connolly.

Image of the microfluidic device developed to determine activity-dependent spreading neurotoxic and neuroprotective signaling. Five parallel cell culture chambers recreate in vivo disease conditions. NeuroscienceNews.com image is adapted from the University of Strathclyde press release.

Doctor Connolly worked on the project with Doctor Michele Zagnoni, Senior Lecturer in Electronic and Electrical Engineering at the University of Strathclyde.

Doctor Zagnoni said, “Using microfluidic technology, we were able to produce in-vitro neuronal networks to investigate spreading toxicity in the brain, which is the cause of brain damage even after an initial trauma.

“Through this process we were able to demonstrate how the spread of this toxicity is driven. In doing that we also uncovered a previously unknown, fast acting, neuroprotective signaling mechanism.

“This mechanism utilizes the innate capacity of the surrounding neuronal networks (grown in the laboratory) to provide protection against the spreading toxicity. By stimulating that network, then theoretically we could limit the spread of brain damage. That requires further work, but it is an exciting and important possibility.”



The results of the research are published in the journal Scientific Reports.

The project examined the process known as acute secondary neuronal cell death, which is seen in neurodegenerative disease, cerebral ischemia (stroke) and traumatic brain injury (TBI) and drives spreading neurotoxicity into surrounding, undamaged, brain areas.

Source: University of Strathclyde.

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Neurons Compete to Form Memories

The same populations of brain cells encode memories that occur close together in time, according to new research.

Scientists have made significant progress toward understanding how individual memories are formed, but less is known about how multiple memories interact. Researchers from the Hospital for Sick Children in Toronto and colleagues studied how memories are encoded in the amygdalas of mice. Memories formed within six hours of each other activate the same population of neurons, whereas distinct sets of brain cells encode memories formed farther apart, in a process whereby neurons compete with their neighbors, according to the team’s study, published today (July 21) in Science.

“Some memories naturally go together,” study coauthor Sheena Josselyn of the Hospital for Sick Children told The Scientist. For example, you may remember walking down the aisle at your wedding ceremony and, later, your friend having a bit too much to drink at the reception. “We’re wondering about how these memories become linked in your mind,” Josselyn said.



When the brain forms a memory, a group of neurons called an “engram” stores that information. Neurons in the lateral amygdala—a brain region involved in memory of fearful events—are thought to compete with one another to form an engram. Cells that are more excitable or have higher expression of the transcription factor CREB—which is critical for the formation of long-term memories—at the time the memory is being formed will “win” this competition and become part of a memory.

Josselyn and colleagues wondered whether two memories that are formed close together in time activated the same or distinct engrams. They trained mice to associate a specific sound with a foot shock and, later, another sound with a foot shock. When presented with the sounds alone, the animals would freeze a sign that they had formed fear memories. The mice were then sacrificed, and their brains were removed for further study. The researchers measured the expression of two genes, arc and homer1a (h1a), using fluorescent in situ hybridization. These genes label neurons that were active in the previous five minutes and 30 to 40 minutes, respectively.

The same population of neurons was active if the two memories were formed within 1.5 to six hours of each other, but not if they were formed within 18 to 24 hours of each other, Josselyn and colleagues found.



When the researchers “extinguished” an animal’s second memory by presenting the sound in the absence of a foot shock, the mouse no longer froze when it heard that sound. But it also froze less in response to hearing the first sound if the memories had been formed within six hours of each other, suggesting the two memories had become linked.

Next, Josselyn’s team manipulated the excitability of the neurons in the animals’ amygdalas using optogenetics. The researchers infected neurons in the animals’ lateral amygdalas with a herpes virus that caused the cells to express channel rhodopsin. By shining blue or red light on these neurons, the team could excite or inhibit them, respectively. The researchers attempted to artificially link two memories formed 24 hours apart by increasing the excitability of the same population of neurons before both memories were formed. When they then inhibited these cells, both memories were impaired, indicating a successful linkage.

Next the researchers tried to separate two memories formed close together in time by exciting neurons before the first memory was formed and inhibiting excitability before the formation of the second. But they found that suppressing the neurons involved in the first memory also disrupted the second memory. The researchers found similar results by increasing or decreasing the expression of CREB.
“Linking two memories was very easy, but trying to separate memories that were normally linked became very difficult,” Josselyn said.

Finally, the researchers manipulated the excitability of interneurons in the lateral amygdala, showing that neurons that successfully make it into an engram do so by competing with their neighbors. These neurons also temporarily suppress other cells from being allocated to another memory, in a winner-takes-all competition.



“This is an impressive study showing compelling evidence for a linkage between memories encoded in the lateral amygdala about similar threatening events that occur close in time,” neuroscientist Joseph LeDoux of New York University, who was not involved in the study, wrote in an email to The Scientist.

In May, researchers from the University of California, Los Angeles (UCLA), reported similar results in the hippocampi of mice. There was greater overlap between neurons in this area that encoded memories formed within the same day, compared with ones formed a week apart, the group showed.

“Our two papers carried out studies in two different brain regions [hippocampus and amygdala], and with very different tools, but we found very similar results as to how memories are connected across time,” UCLA’s Alcino Silva, a coauthor on the May study who has previously collaborated with Josselyn, wrote in an email to. The Scientist. “The fact that two very different brain regions share this same mechanism points to the universality of this mechanisms,” Silva added.

It makes sense that the brain would link together memories that are formed close together, Josselyn noted. The process could also explain what goes awry in conditions like schizophrenia, in which the brain abnormally links thoughts and memories.



“But before we go on to treat memory disorders, we really need to understand the basics,” she said.

Source: Tanya Lewis

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