When food porn holds no allure: the science behind satiety

New research from the University of British Columbia is shedding light on why enticing pictures of food affect us less when we’re full.

“We’ve known that insulin plays a role in telling us we’re satiated after eating, but the mechanism by which this happens is unclear,” says Stephanie Borgland, an assistant professor in UBC’s Dept. of Anesthesiology, Pharmacology and Therapeutics and the study’s senior author.

In the new study published online this week in Nature Neuroscience, Borgland and colleagues found that insulin – prompted by a sweetened, high-fat meal – affects the ventral tegmental area (VTA) of the brain, which is responsible for reward-seeking behaviour. When insulin was applied to the VTA in mice, they no longer gravitated towards environments where food had been offered.

“Insulin dulls the synapses in this region of the brain and decreases our interest in seeking out food,” says Borgland, “which in turn causes us to pay less attention to food-related cues.”

“There has been a lot of discussion around the environmental factors of the obesity epidemic,” Borgland adds, pointing to fast food advertising bans in Quebec, Norway, the U.K., Greece and Sweden. “This study helps explain why pictures or other cues of food affect us less when we’re satiated – and may help inform strategies to reduce environmental triggers of overeating.”

The VTA has also been shown to be associated with addictive behaviours, including illicit drug use. Borgland says better understanding of the mechanism in this region of the brain could, in the long run, inform diagnosis and treatment.

(Image: Shutterstock)

Glial cells assist in the repair of injured nerves

Unlike the brain and spinal cord, the peripheral nervous system has an astonishing capacity for regeneration following injury. Researchers at the Max Planck Institute of Experimental Medicine in Göttingen have discovered that, following nerve damage, peripheral glial cells produce the growth factor neuregulin1, which makes an important contribution to the regeneration of damaged nerves.

From their cell bodies to their terminals in muscle or skin, neuronal extensions or axons in the peripheral nervous system are surrounded along their entire length by glial cells. These cells, which are known as Schwann cells, envelop the axons with an insulating sheath called myelin, which enables the rapid transmission of electrical impulses. Following injury to a peripheral nerve, the damaged axons degenerate. After a few weeks, however, they regenerate and are then recovered with myelin by the Schwann cells. For thus far unexplained reasons, however, the Schwann cells do not manage to regenerate the myelin sheaths completely. Thus the function of damaged nerves often remains permanently impaired and certain muscles remain paralysed in affected patients.

In a current research study, the scientists have succeeded in showing that the growth factor neuregulin1 supports nerve repair and the redevelopment of the myelin layer. This protein is usually produced by neurons and is localised on axons where it acts as an important signal for the maturation of Schwann cells and myelin formation. Because the axons rapidly degenerate after injury, the remaining Schwann cells lose their contact with the axons. They thus lack the neuregulin1 signal of the nervous fibres. “In the phase following nerve damage, in which the axons are missing, the Schwann cells must carry out many tasks without the help of axonal signals. If the Schwann cells cannot overcome this first major obstacle in the aftermath of nerve injury, the nerve cannot be adequately repaired,” explains Ruth Stassart, one of the study authors.

To prevent this, the Schwann cells themselves take over the production of the actual neuronal signal molecule. After nerve damage, they synthesise the neuregulin1 protein until the axons have grown again. With the help of genetically modified mice, the researchers working on this study were able to show that the neuregulin1 produced in Schwann cells is necessary for the new maturation of the Schwann cells and the regeneration of the myelin sheath after injury. “In mice that lack the neuregulin1 gene in their Schwann cells, the already incomplete nerve regeneration process is extensively impaired,” explains co-author Robert Fledrich.

The researchers would now like to examine in greater detail how the Schwann cells contribute to the complete repair of myelinated axons after nerve damage, so that this information can also be used for therapeutic purposes.

Neuroscientists pinpoint location of fear memory in amygdala

A rustle of undergrowth in the outback: it’s a sound that might make an animal or person stop sharply and be still, in the anticipation of a predator. That “freezing” is part of the fear response, a reaction to a stimulus in the environment and part of the brain’s determination of whether to be afraid of it.

A neuroscience group at Cold Spring Harbor Laboratory (CSHL) led by Assistant Professor Bo Li Ph.D., together with collaborator Professor Z. Josh Huang Ph.D., today release the results of a new study that examines the how fear responses are learned, controlled, and memorized. They show that a particular class of neurons in a subdivision of the amygdala plays an active role in these processes.

Locating fear memory in the amygdala

Previous research had indicated that structures inside the amygdalae, a pair of almond-shaped formations that sit deep within the brain and are known to be involved in emotion and reward-based behavior, may be part of the circuit that controls fear learning and memory. In particular, a region called the central amygdala, or CeA, was thought to be a passive relay for the signals relayed within this circuit.

Li’s lab became interested when they observed that neurons in a region of the central amygdala called the lateral subdivision, or CeL, “lit up” in a particular strain of mice while studying this circuit.

“Neuroscientists believed that changes in the strength of the connections onto neurons in the central amygdala must occur for fear memory to be encoded,” Li says, “but nobody had been able to actually show this.”

This led the team to further probe into the role of these neurons in fear responses and furthermore to ask the question: If the central amygdala stores fear memory, how is that memory trace read out and translated into fear responses?

To examine the behavior of mice undergoing a fear test the team first trained them to respond in a Pavlovian manner to an auditory cue. The mice began to “freeze,” a very common fear response, whenever they heard one of the sounds they had been trained to fear.

To study the particular neurons involved, and to understand them in relation to the fear-inducing auditory cue, the CSHL team used a variety of methods. One of these involved delivering a gene that encodes for a light-sensitive protein into the particular neurons Li’s group wanted to look at.

By implanting a very thin fiber-optic cable directly into the area containing the photosensitive neurons, the team was able to shine colored laser light with pinpoint accuracy onto the cells, and in this manner activate them. This is a technique known as optogenetics. Any changes in the behavior of the mice in response to the laser were then monitored.

A subset of neurons in the central amygdala controls fear expression

The ability to probe genetically defined groups of neurons was vital because there are two sets of neurons important in fear-learning and memory processes. The difference between them, the team learned, was in their release of message-carrying neurotransmitters into the spaces called synapses between neurons. In one subset of neurons, neurotransmitter release was enhanced; in another it was diminished. If measurements had been taken across the total cell population in the central amygdala, neurotransmitter levels from these two distinct sets of neurons would have been averaged out, and thus would not have been detected.

Li’s group found that fear conditioning induced experience-dependent changes in the release of neurotransmitters in excitatory synapses that connect with inhibitory neurons – neurons that suppress the activity of other neurons – in the central amygdala. These changes in the strength of neuronal connections are known as synaptic plasticity.

Particularly important in this process, the team discovered, were somatostatin-positive (SOM+) neurons. Somatostatin is a hormone that affects neurotransmitter release. Li and colleagues found that fear-memory formation was impaired when they prevent the activation of SOM+ neurons.

SOM+ neurons are necessary for recall of fear memories, the team also found. Indeed, the activity of these neurons alone proved sufficient to drive fear responses. Thus, instead of being a passive relay for the signals driving fear learning and responses in mice, the team’s work demonstrates that the central amygdala is an active component, and is driven by input from the lateral amygdala, to which it is connected.

“We find that the fear memory in the central amygdala can modify the circuit in a way that translates into action — or what we call the fear response,” explains Li.

In the future Li’s group will try to obtain a better understanding of how these processes may be altered in post-traumatic stress disorder (PTSD) and other disorders involving abnormal fear learning. One important goal is to develop pharmacological interventions for such disorders.

Li says more research is needed, but is hopeful that with the discovery of specific cellular markers and techniques such as optogenetics, a breakthrough can be made.

Mediterranean diet may not protect brain

Hopes that a Mediterranean diet would be as good for the head as it is for the heart may have been dampened by a French study that found little benefit for aging brains from the diet rich in fruit, vegetables, whole grains, nuts, wine and olive oil.

The study, published in the American Journal of Clinical Nutrition, looked at the participants’ dietary patterns in middle age and measured their cognitive performance at around age 65, but found no connection between Mediterranean eating and mental performance.

"Our study does not support the hypothesis of a significant neuroprotective effect of a (Mediterranean diet) on cognitive function," writes study leader Emmanuelle Kesse-Guyot at the nutritional epidemiology research centre of the French national health research agency INSERM.

It’s been suggested that the “good” fats in the Mediterranean diet might benefit the brain directly, or that low saturated fats and high fiber in the diet could help stave off cognitive decline indirectly by keeping blood vessels healthy.

Previous research has seemed to uphold that premise.

One large study in the US Midwest, for example, found that people in their 60s and older who ate a mostly Mediterranean diet were less prone to mental decline as they aged. Another study of residents of Manhattan linked a Mediterranean-style diet to a 40 per cent lower risk of Alzheimer’s disease.

No significant difference

Researchers in the French study used data on 3083 people who were followed from the mid-1990s, when they were at least 45 years old.

At the beginning of the study, participants recorded what they ate over one 24-hour period every two months, for a total of six dietary record samples per year. Then, between 2007 and 2009 when the participants were about 65 years old, their memory and other mental abilities were measured.

Researchers then separated participants into three categories depending on how closely they adhered to a Mediterranean-style diet, and compared their mental ability test scores.

Overall, they found that people who ate a diet closest to the Mediterranean ideal performed about the same as those who ate a non-restricted diet.

Associate Professor Nikos Scarmeas, of New York’s Columbia University Medical Center, was not involved with the study but has researched the effects of food on brain health. He says it’s important to note that the new study had some limitations.

For instance, researchers only tested the participants’ mental abilities once, making it impossible to track whether they got better or worse over time, adds Scarmeas.

"We don’t have the strong evidence to go and tell people, ‘Listen, if you follow this diet, it will improve cognition’," he says.

(Image: mediterraneandiet.com)

Poor sleep in old age prevents the brain from storing memories

The connection between poor sleep, memory loss and brain deterioration as we grow older has been elusive. But for the first time, scientists at the University of California, Berkeley, have found a link between these hallmark maladies of old age. Their discovery opens the door to boosting the quality of sleep in elderly people to improve memory.

UC Berkeley neuroscientists have found that the slow brain waves generated during the deep, restorative sleep we typically experience in youth play a key role in transporting memories from the hippocampus – which provides short-term storage for memories – to the prefrontal cortex’s longer term “hard drive.”

However, in older adults, memories may be getting stuck in the hippocampus due to the poor quality of deep ‘slow wave’ sleep, and are then overwritten by new memories, the findings suggest.

“What we have discovered is a dysfunctional pathway that helps explain the relationship between brain deterioration, sleep disruption and memory loss as we get older – and with that, a potentially new treatment avenue,” said UC Berkeley sleep researcher Matthew Walker, an associate professor of psychology and neuroscience at UC Berkeley and senior author of the study published in the journal Nature Neuroscience.

Study Sheds Light on the Complexity of Gene Therapy for Congenital Blindness

Independent clinical trials, including one conducted at the Scheie Eye Institute at the Perelman School of Medicine, have reported safety and efficacy for Leber congenital amaurosis (LCA), a congenital form of blindness caused by mutations in a gene (RPE65) required for recycling vitamin A in the retina. Inherited retinal degenerative diseases were previously considered untreatable and incurable. There were early improvements in vision observed in the trials, but a key question about the long-term efficacy of gene therapy for curing the retinal degeneration in LCA has remained unanswered. Now, new research from the Scheie Eye Institute, published this week in the Proceedings of the National Academy of Sciences, finds that gene therapy for LCA shows enduring improvement in vision but also advancing degeneration of affected retinal cells, both in LCA patients and animal models of the same condition.

LCA disease from RPE65 mutations has two-components: a biochemical blockade leading to impaired vision, and a progressive loss of the light-sensing photoreceptor cells throughout life of the affected patient. The authors of the new study explain that until now gene therapy has been optimistically assumed, but not proven, to solve both disease components at the same time.

“We all hoped that the gene injections cured both components – re-establishing the cycle of vision and also preventing further loss of cells to the second disease component” said Artur V. Cideciyan, PhD, lead author and co-investigator of an LCA clinical trial at Penn.

Yet, when the otherwise invisible cell layers of the retina were measured by optical imaging in clinical trial participants serially over many years, the rate of cell loss was the same in treated and untreated regions. “In other words, gene therapy improved vision but did not slow or halt the progression of cell loss,” commented Cideciyan.

“These unexpected observations should help to advance the current treatment by making it better and longer lasting,” commented co-author Samuel G. Jacobson, MD, PhD, principal investigator of the clinical trial. “Slowing cell loss in different retinal degenerations has been a major research direction long before the current gene therapy trials. Now, the two directions must converge to ensure the longevity of the beneficial visual effects in this form of LCA.”

(Image: bigstockphoto)

Evidence Mounts for Role of Mutated Genes in Development of Schizophrenia

Johns Hopkins researchers have identified a rare gene mutation in a single family with a high rate of schizophrenia, adding to evidence that abnormal genes play a role in the development of the disease.

The researchers, in a report published in the journal Molecular Psychiatry, say that family members with the mutation in the gene Neuronal PAS domain protein 3 (NPAS3) appear at high risk of developing schizophrenia or another debilitating mental illnesses.

Normally functioning NPAS3 regulates the development of healthy neurons, especially in a region of the brain known as the hippocampus, which appears to be affected in schizophrenia. The Johns Hopkins researchers say they have evidence that the mutation found in the family may lead to abnormal activity of NPAS3, which has implications for brain development and function.

"Understanding the molecular and biological pathways of schizophrenia is a powerful way to advance the development of treatments that have fewer side effects and work better than the treatments now available," says study leader Frederick C. Nucifora Jr., Ph.D., D.O., M.H.S., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "We could definitely use better medicines."

Cell biologists show molecular forces are key to proper cell division

Studies led by assistant professor of Biology Thomas Maresca are revealing new details about a molecular surveillance system that helps detect and correct errors in cell division that can lead to cell death or human diseases. Findings are reported in the current issue of the Journal of Cell Biology.

The purpose of cell division is to evenly distribute the genome between two daughter cells. To achieve this, every chromosome must properly interact with a football-shaped structure called the spindle. However, interaction errors between the chromosomes and spindle during division are amazingly common, occurring in 86 to 90 percent of chromosomes, says Maresca, an expert in mitosis.

“This is not quite so surprising when you realize that every single one of the 46 chromosomes has to get into perfect position every time a cell divides,” he notes. The key to flawless cell division is to correct dangerous interactions before the cell splits in two.

Working with fruit fly tissue culture cells, Maresca and graduate students Stuart Cane and Anna Ye have developed a way to watch and record images of the key players in cell division including microtubule filaments that form the mitotic spindle and sites called kinetochores that mediate chromosome-microtubule interactions. They also examined the contribution of a force generated by molecular engines called the polar ejection force (PEF), which is thought to help line up the chromosomes in the middle of the spindle for division. For the first time, they directly tested and quantified how PEF, in particular, influences tension at kinetochores and affects error correction in mitosis.

“We also now have a powerful new assay to get at how this tension regulates kinetochore-microtubule interactions,” Maresca adds. “We knew forces and tension regulated this process, but we didn’t understand exactly how. With the new technique, we can start to dissect out how tension modulates error correction to repair the many erroneous attachment intermediates that form during division.”

Stroke Survivors with PTSD More Likely to Avoid Treatment

A new survey of stroke survivors has shown that those with post-traumatic stress disorder (PTSD) are less likely to adhere to treatment regimens that reduce the risk of an additional stroke. Researchers found that 65 percent of stroke survivors with PTSD failed to adhere to treatment, compared with 33 percent of those without PTSD. The survey also suggests that nonadherence in PTSD patients is partly explained by increased ambivalence toward medication. Among stroke survivors with PTSD, approximately one in three (38 percent) had concerns about their medications. Results of the study, led by Columbia University Medical Center researchers, are published today in the British Journal of Health Psychology.

According to data from the American Stroke Association, nearly 795,000 Americans each year suffer a new or recurrent stroke. Stroke is the fourth-leading cause of death and the top cause of disability in the United States. Survivors of strokes are often prescribed treatment regiments, including antiplatelet agents, antihypertensive agents, and statins, which help reduce the risk of subsequent strokes. Previous research has shown that PTSD triggered by medical events—which affects 18 percent of stroke survivors—may impair recovery.

“Unfortunately, too many stroke survivors are not compliant with these regimens, even though we know that adherence to post-stroke treatment regimens is one of the most important components of reducing the risk of a future stroke,” said Ian M. Kronish, MD, MPH, assistant professor of medicine (Center for Behavioral Cardiovascular Health) and one of the study’s authors.

“For those with PTSD, this study shows that concerns about medications are a significant barrier to treatment adherence. Stroke survivors should be assessed for concerns about medications and PTSD symptoms, so that interventions may be introduced as early as possible to get patients back on track to avoid future stroke events.”