Carnosine And Raw Veganism

Posted by Andrea Lewis

 Carnosine is an important nutrient that is gaining greater attention, due to dozens of research studies that have demonstrated its wide range of health benefits. There’s just one caveat: carnosine is only found as carnosine in fish, beef, poultry and pork. And yet, ironically, the animals that are considered the best sources of this nutrient do not themselves consume animals. So, where are they getting their carnosine from? The same place that vegans are getting theirs: whole foods.

Carnosine, which is concentrated in the brain and muscle tissues, is a dipeptide of the amino acids beta-alanine and histidine. And while carnosine, in its whole dipeptide form, is only found in meat, both of its constituents are found in a wide variety of plant foods. This is the most logical explanation for how animals like cows, turkeys, chickens and pigs come to have so much in their tissues, especially when one considers how carnosine in meat is broken down and used in the body.

Carnosine Digestion and Synthesis

Upon digestion, carnosine is broken down in the gastrointestinal tract into its constituents. Yes, some intact carnosine does escape the GI tract freely but that small amount is quickly broken down in the blood by the enzyme carnosinase. Carnosinase hydrolyzes carnosine and other dipeptides containing histidine into their constituent amino acids. In other words, after consuming meat, all of the carnosine that was ingested is converted to beta-alanine and histidine. Then, oddly enough, the amino acids are converted back to carnosine in the muscles and used or transported where needed. The entire process of carnosine synthesis is not entirely understood, but it’s worth noting that consuming carnosine from meat is unnecessary, as it will be converted into beta-alanine and histidine anyway, both of which are available in many raw whole foods.

Carnosine Benefits

Carnosine’s main claim to fame is its ability to inhibit AGE (Advanced Glycation End) products, which is valuable for treating and preventing a range of diseases. This benefit is largely responsible for carnosine’s other health benefits and uses:

  • Anti-oxidant
  • Heart health
  • Diabetes
  • Kidney health
  • Atherosclerosis
  • Eye health
  • Improved cognitive function
  • Autism Spectrum Disorder

Carnosine has been shown to reduce and protect against oxidative stress in the body, making it an excellent anti-oxidant. This anti-oxidant protection extends to pH buffering and electrolyte support, which is highly beneficial to heart health. The heart is a fast twitch muscle that demands a lot of energy, but it does not get the same amount of rest as the other fast twitch muscles in the body. The heart must always be active or, obviously, we die. As a result, the heart requires more carnosine to engage in faster, efficient muscle contractions. Heart tissue must also have the right electrolyte balance, pH buffers, and plenty of antioxidants to manage daily demands at an optimal level; carnosine helps to provide all of the above. Studies have shown that individuals with myocardial infarction, bundle branch blocks, angina, congestive heart failure (CHF), and other cardiomyopathies may benefit from increasing their intake of carnosine. One such study, ‘β-Alanine and orotate as supplements for cardiac protection’, published in the journal Open Heart, showed that carnosine, synthesized in the body from beta-alanine, is indeed more concentrated in fast twitch muscles, like the heart, and can help protect against cardiac issues, such as congestive heart failure.

Diabetics tend to have elevated levels of oxidative stress stemming from their condition. Diabetics also tend to have pronounced issues with atherosclerosis and kidney disease, because diabetes causes a stiffening of tissues as a result of excess AGEs in the body; that excess has been linked to a lack of carnosine. The same holds true for some optical issues. Carnosine helps protect the eye from oxidative damage of the lens and retina. One animal study, in particular, demonstrated that carnosine protected the retina from restriction in blood supply (oxygenation) when the eye tissue was under increased intraoccular pressure, which reduces the risk for glaucoma. Carnosine is also available in an eye drop solution for those at risk for glaucoma and cataracts. For more information on that topic, Google ‘carnosine eye drops’, there are a lot of blogs and research papers on the topic.

Carnosine has been studied extensively in the muscles and brain tissues, because that’s where it’s concentrated. In regards to brain and neurological health, carnosine has been shown to be of great help in preventing and reversing cognitive decline. And it’s affect on the brain and muscles appears more perceptible in the elderly. One study in particular, ‘Anserine and carnosine supplementation in the elderly: Effects on cognitive functioning and physical capacity’, published in the Archive of Gerontology and Geriatrics, Sept-Oct. 2014, showed that while cognitive function and physical capacity increased, BMI, blood pressure and heart rate improved during the 13-week study, in which fifty-one subjects were given Chicken meat extract containing CRC components (2:1 ration of anserine to carnosine). FYI, anserine is also a dipeptide that contains beta-alanine and histidine. A quote from the study, “After supplementation Body Mass Index (BMI) decreased significantly (p<0.05) in the CRC group performance comparing the placebo group. In two of six Senior Fitness Test the scores increased significantly (p<0.05) in CRC group comparing to the placebo group. The perceived exertion differed significantly (p<0.05) at the baseline and after follow up at the CRC group. The mean values of the Short Test of Mental Status (STMS) scores showed the significant (p<0.04) increase only in CRC group, in the subscores of construction/copying, abstraction and recall. Conducted anserine and carnosine supplementation in the elderly brings promising effects on cognitive functioning and physical capacity of participants. However, further studies are needed.”

Another study, entitled ‘Carnosine Treatment for Gulf War Illness: A Randomized Controlled Trial’, published in the Journal of Health Sciences, Vol. 5, No. 3, 2013, showed that carnosine was also able to treat cognitive and some physical issues in gulf war veterans. “About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI). A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species (ROS) and central nervous system injury. The endogenous antioxidant L-carnosine (B-alanyl-L-histidine) is a potential treatment since it is a free radical scavenger in nervous tissue. To determine if nutritional supplementation with L-carnosine would significantly improve pain, cognition and fatigue in GWI, a randomized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed.

“L-carnosine was given as 500, 1000, and 1500 mg increasing at 4 week intervals. Outcomes included subjective fatigue, pain and psychosocial questionnaires, and instantaneous fatigue and activity levels recorded by ActiWatch Score devices. Cognitive function was evaluated by WAIS-R digit symbol substitution test.

“Carnosine had 2 potentially beneficial effects: WAIS-R scores increased significantly, and there was a decrease in diarrhea associated with irritable bowel syndrome. No other significant incremental changes were found. Therefore, 12 weeks of carnosine (1500 mg) may have beneficial cognitive effects in GWI. Fatigue, pain, hyperalgesia, activity and other outcomes were resistant to treatment.”

Carnosine has the ability to cross the blood-brain barrier, the brain’s security system, which is essentially a network of blood vessels that only permit essential nutrients to enter while blocking other substances. This has been an obstacle to treating many neurological issues, including seizures and Autism Spectrum Disorder. In animal studies, carnosine has been shown to improve management of seizures, acting as an anticonvulsant. One study, published in Brain Research, November 6, 2008, examined the effect of carnosine on epilepsy in rats. The epileptic episodes were induced by penicillin. The scientists ascertained that “These findings indicate that carnosine has an anticonvulsant effect on penicillin-induced epilepsy in rats. Thus, our data support the hypothesis that carnosine may be a potential anticonvulsant drug for clinical therapy of epilepsy in the future.” Later studies supported their findings. An article published in Nutrition Review, April 19, 2013, reported that carnosine improved language skills and behavior in children with ASD (Autistic Spectrum Disorder). “Researchers treated 31 autistic children, ranging from 3 to 12 years in age, with either 400 mg of L-Carnosine, twice a day, or a placebo, for 8 weeks. At the end of the study the children treated with L-Carnosine showed significant improvements in behavior, socialization, and communication, as well as increases in language comprehension based on CARS (Childhood Autism Rating Scale), vocabulary tests (E/ROWPVT) and biweekly parent reports. In the conclusion to their report the researchers state, “Oral supplementation with L-Carnosine resulted in demonstrable improvements in autistic behaviors, as well as increases in language comprehension that reached statistical significance.” … the researchers report that L-Carnosine may improve receptive language, auditory processing, socialization, awareness of surroundings, and even help fine motor planning and expressive language when compared to placebo. Responses are usually seen between one to eight weeks after beginning treatment.” The study referenced in the article is titled ‘Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders’, and was published in the Journal of Child Neurology, November 17, 2002.

What About Histidine?

All of the carnosine studies I found (including those mentioned and quoted above) used either beta-alanine supplements, l-carnosine supplements or carnosine extracted directly from poultry, but histidine is also required for synthesis of carnosine in the body. I assume, because the nutrient is so prevalent in such a wide variety of foods, that the researchers saw no need to use a histidine supplement as part of their carnosine research studies when using beta-alanine supplements. Histidine can be found in both animals and plants, as well as every tissue in the human body; even the myelin sheaths that coat nerve cells and ensure the transmission of messages from the brain to various parts of the body contain histidine. So, whether one is a vegan, vegetarian or carnivore, they are sure to get sufficient amounts of histidine in their diet.

Best Whole Food Sources of Beta-Alanine

  • Soy beans / soy nuts
  • Edamame
  • Asparagus
  • Turnip greens
  • White mushrooms
  • Watercress
  • Laver seaweed
  • Spirulina seaweed

Best Whole Food Sources of Histidine

  • Edamame
  • Green peas
  • Asparagus
  • soybean sprouts
  • Broccoli
  • Mustard Greens
  • Spinach
  • Sweet corn
  • Garlic
  • Cabbage
  • Eggplants
  • Celery
  • Onions
  • Carrots
  • Bamboo shoots
  • Cauliflower
  • Daikon (Japanese radish)
  • Pumpkin
  • Okra pods
  • Head lettuce / Butter lettuce
  • Lotus root
  • Chinese chives
  • Green sweet peppers
  • Chinese cabbage
  • Tomatoes
  • Cucumbers

Obviously, there are far more histidine-rich whole foods than beta-alanine-rich whole foods, and I didn’t even list half of the whole foods that contain histidine. Apparently, most foods contain histidine, including those used to feed livestock and, of course, the livestock themselves. And it’s worth noting that histidine, in addition to being half of the peptide bond that forms carnosine and its pivotal role in the formation of protein, has demonstrated a variety of therapeutic properties both anecdotally and in clinical studies; those properties include reducing the effects of stress and chronic conditions like rheumatoid arthritis, treating certain types of sexual dysfunction, fighting fatigue and preventing anemia. In any case, it’s good to know that one can indeed get all of the benefits of carnosine and its constituent elements as a raw vegan.

New evidence that chronic stress predisposes brain to mental illness

By Robert Sanders

University of California, Berkeley, researchers have shown that chronic stress generates long-term changes in the brain that may explain why people suffering chronic stress are prone to mental problems such as anxiety and mood disorders later in life.

myelin

Myelin is stained blue in this cross section of a rat hippocampus. Myelin, which speeds electrical signals flowing through axons, is produced by oligodendrocytes, which increase in number as a result of chronic stress. New oligodendrocytes are shown in yellow. Image by Aaron Friedman and Daniela Kaufer.

Their findings could lead to new therapies to reduce the risk of developing mental illness after stressful events.

Doctors know that people with stress-related illnesses, such as post-traumatic stress disorder (PTSD), have abnormalities in the brain, including differences in the amount of gray matter versus white matter. Gray matter consists mostly of cells – neurons, which store and process information, and support cells called glia – while white matter is comprised of axons, which create a network of fibers that interconnect neurons. White matter gets its name from the white, fatty myelin sheath that surrounds the axons and speeds the flow of electrical signals from cell to cell.

How chronic stress creates these long-lasting changes in brain structure is a mystery that researchers are only now beginning to unravel.

In a series of experiments, Daniela Kaufer, UC Berkeley associate professor of integrative biology, and her colleagues, including graduate students Sundari Chetty and Aaron Freidman, discovered that chronic stress generates more myelin-producing cells and fewer neurons than normal. This results in an excess of myelin – and thus, white matter – in some areas of the brain, which disrupts the delicate balance and timing of communication within the brain.

“We studied only one part of the brain, the hippocampus, but our findings could provide insight into how white matter is changing in conditions such as schizophrenia, autism, depression, suicide, ADHD and PTSD,” she said.

The hippocampus regulates memory and emotions, and plays a role in various emotional disorders.

Kaufer and her colleagues published their findings in the Feb. 11 issue of the journal Molecular Psychiatry.

Does stress affect brain connectivity?

Kaufer’s findings suggest a mechanism that may explain some changes in brain connectivity in people with PTSD, for example. One can imagine, she said, that PTSD patients could develop a stronger connectivity between the hippocampus and the amygdala – the seat of the brain’s fight or flight response – and lower than normal connectivity between the hippocampus and prefrontal cortex, which moderates our responses.

“You can imagine that if your amygdala and hippocampus are better connected, that could mean that your fear responses are much quicker, which is something you see in stress survivors,” she said. “On the other hand, if your connections are not so good to the prefrontal cortex, your ability to shut down responses is impaired. So, when you are in a stressful situation, the inhibitory pathways from the prefrontal cortex telling you not to get stressed don’t work as well as the amygdala shouting to the hippocampus, ‘This is terrible!’ You have a much bigger response than you should.”

white-m

 

 

She is involved in a study to test this hypothesis in PTSD patients, and continues to study brain changes in rodents subjected to chronic stress or to adverse environments in early life.

Stress tweaks stem cells

Kaufer’s lab, which conducts research on the molecular and cellular effects of acute and chronic stress, focused in this study on neural stem cells in the hippocampus of the brains of adult rats. These stem cells were previously thought to mature only into neurons or a type of glial cell called an astrocyte. The researchers found, however, that chronic stress also made stem cells in the hippocampus mature into another type of glial cell called an oligodendrocyte, which produces the myelin that sheaths nerve cells.

The finding, which they demonstrated in rats and cultured rat brain cells, suggests a key role for oligodendrocytes in long-term and perhaps permanent changes in the brain that could set the stage for later mental problems. Oligodendrocytes also help form synapses – sites where one cell talks to another – and help control the growth pathway of axons, which make those synapse connections.

The fact that chronic stress also decreases the number of stem cells that mature into neurons could provide an explanation for how chronic stress also affects learning and memory, she said.

Kaufer is now conducting experiments to determine how stress in infancy affects the brain’s white matter, and whether chronic early-life stress decreases resilience later in life. She also is looking at the effects of therapies, ranging from exercise to antidepressant drugs, that reduce the impact of stress and stress hormones.

Kaufer’s coauthors include Chetty, formerly from UC Berkeley’s Helen Wills Neuroscience Institute and now at Harvard University; Friedman and K. Taravosh-Lahn at UC Berkeley’s Department of Integrative Biology; additional colleagues from UC Berkeley and others from Stanford University and UC Davis.

The work was supported by a BRAINS (Biobehavioral Research Awards for Innovative New Scientists) award from the National Institute of Mental Health of the National Institutes of Health (R01 MH087495), a Berkeley Stem Cell Center Seed Grant, the Hellman Family Foundation and the National Alliance for Research on Schizophrenia and Depression.

RELATED INFORMATION

Stress-induced arousal impairs long term memory

A University of Virginia study was conducted to determine if stress enhance or impair memory Consolidation.

Overall results provide consistent evidence that stress does not uniformly enhance memory consolidation. Although prior research has shown that stress during recall can interfere with memory, the current experiments obtained evidence of interference when stress was introduced after learning and participants had returned to baseline levels of arousal before recall. This is the first evidence of which the authors are aware that stress can actually impair consolidation of declarative memories. We tested several hypotheses for these effects, including those concerned with stimulus type, rehearsal, gender, hormonal influences (from menstrual cycle and oral contraceptive use), and opportunity for post-encoding processing. Nevertheless, we continued to obtain the same robust finding that stress-induced arousal impairs long term memory.

In each experiment, exposure to a stressor interfered with, rather than enhanced, long term memory for associated material.


Another was conducted to determine if chronic stress induces a hyporeactivity of the autonomic nervous system in response to acute mental stressor and impairs cognitive performance in business executives.

The study is the first to demonstrate a blunted reactivity of the ANS when male subjects with chronic psychological stress were subjected to an acute mental stressor, and this change could contribute to impairments in cognitive performance.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373764/


Another study also demonstrated that it is better not to deal with two tasks at the same time when stressed since acute psychosocial stress reduces task shielding in dual-task performance.

Following successful stress induction, as indicated by increases in salivary α-amylase (sAA) and cortisol that reflect increases in sympathetic nervous system and hypothalamus-pituitary-adrenal (HPA) axis activity, respectively, stressed individuals displayed reduced task shielding relative to controls. This result was further substantiated by a correlation between treatment-related increase in cortisol, but not sAA, and between-task interference, suggesting a potential role of the HPA stress response for the development of the observed effects. As an additional finding, when the volunteers were categorized with regard to their action-state orientation, their orientation did not interact with stress but did reveal generally increased between-task interference, and thus inferior task shielding, for state-oriented as compared to action-oriented individuals.


Connie’s comments: Chronic stress, experiencing stressors over a prolonged period of time, can result in a long-term drain on the body.


Nutrition and healing ways for complusiveness, trouble sleeping – supplements to boost Serotonin

  • 5HTP (natural sources)  +Green tea
  • Inositol
  • Saffron
  • L-tryptophan
  • St John’s Wort
  • Exercise
  • DHA Omega 3
  • Smart carbohydrate diet
  • Learn to remove or distance from worrying thoughts

Nutrition and healing ways for impulsiveness, prone to obesity – supplements to boost Dopamine

  • 5HTP (natural sources)  +Green tea
  • L-tyrosine
  • Rhodiola
  • Ginseng
  • Zinc
  • Ferritin

 

 

MRI Scans Detect “Brain Rust” in Schizophrenia

Summary: According to a new study, the brain blocks the ability for creating new memories shortly after waking in order to prevent the disruption of the stabilization of memory consolidation that occurs during sleep.

Source: ACNP.

A damaging chemical imbalance in the brain may contribute to schizophrenia, according to research presented at the American College of Neuropsychopharmacology Annual Meeting in Hollywood, Florida.

Using a new kind of MRI measurement, neuroscientists reported higher levels of oxidative stress in patients with schizophrenia, when compared both to healthy individuals and those with bipolar disorder.

“Intensive energy demands on brain cells leads to accumulation of highly reactive oxygen species, such as free radicals and hydrogen peroxide,” according to the study’s lead investigator, Dr. Fei Du, an Assistant Professor of Psychiatry at Harvard Medical School. In schizophrenia, excessive oxidation – which involves the same type of chemical reaction that causes metal to corrode into rust – is widely thought to cause inflammation and cellular damage. However, measuring this process in the living human brain has remained challenging.

Du and colleagues at McLean Hospital measured oxidative stress using a novel magnetic resonance spectroscopy technique. This technique uses MRI scanners to non-invasively measure brain concentrations of two molecules, NAD+ and NADH, that give a readout of how well the brain is able to buffer out excessive oxidants.

Image shows a brain model.

Among 21 patients with chronic schizophrenia, Du observed a 53% elevation in NADH compared to healthy individuals of similar age. A similar degree of NADH elevation was seen in newly diagnosed schizophrenia, suggesting that oxidation imbalance is present even in the early stages of illness. More modest NADH increases were also seen in bipolar disorder, which shares some genetic and clinical overlap with schizophrenia.

In addition to offering new insights into the biology of schizophrenia, this finding also provides a potential way to test the effectiveness of new interventions. “We hope this work will lead to new strategies to protect the brain from oxidative stress and improve brain function in schizophrenia,” Du concludes.

ABOUT THIS SCHIZOPHRENIA RESEARCH ARTICLE

Funding: This work was supported by grants from MH092704 (F.D.); NARSAD (F.D.); NARSAD (D.O.); MH094594 (D.O.); MH104449 (D.O.); Shervert Frazier Research Institute (B.M.C.).

Source: Erin Colladay – ACNP
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: The study will be presented at the 55th Annual Meeting of the American College of Neuropsychopharmacology.

Early Life Social Stress Has Long Term Impact on Brain Networks: Rat Study

Summary: Findings about how early life social stress affect brain connections in mice may have implications for treating human psychiatric illnesses.

Source: Tufts University.

Changes in connectivity in regions of the brain tied to social behavior, stress and depression can inform research on related psychiatric disorders in humans.

Investigators in veterinary and human medicine have uncovered long-term changes in the brains of adult female rats exposed to social stresses early in life, with the biggest impact on regions of the brain that are linked to social behavior, stress, emotion and depression. The findings, which appear online in advance of the January 2017 print edition of Behavioural Brain Research, establish a neural foundation for related imaging work in humans and animals and will enable researchers to begin testing preventative measures and treatments for depression and anxiety.

A team led by Benjamin Nephew, assistant professor at Cummings School of Veterinary Medicine at Tufts University, studied adult female rats exposed to early life chronic social stress (ECSS). Using an ECSS model that was established in Nephew’s previous research on postpartum depression and anxiety, the female rats in the test group were exposed to social stress in their first two weeks of life as pups, while the control group was not exposed to social stress. Previous studies looking at animal models of depression and anxiety have focused primarily on males. The current research can provide important insight into the development of these psychiatric disorders in females.

When the rats reached adulthood (65-90 days old), functional magnetic resonance imaging (fMRI) was administered to measure resting state functional connectivity—the fluctuation in activity in different regions of the brain.

Analysis of the imaging from the ECSS group showed broad changes in activity in areas of the brain that control, among other things, rewards, social behavior, stress and depression. This study was the first to measure resting state functional connectivity in conscious rats in a model of depression. Using fMRI enabled researchers to identify changes in multiple neural circuits simultaneously.

“Conscious rodent imaging allows us to make significant comparisons with human work, as well as integrate past rodent work that focused on individual nuclei to make conclusions about neural networks that control behavior,” said Nephew, the paper’s corresponding author.

Image shows connections in the rat brain.

“Comparing the data from the imaging with clinical models can enhance understanding of susceptibility, resilience, pathological origin and treatment response,” added Dr. Jean King, an author on the study and director of the Center for Comparative NeuroImaging at University of Massachusetts Medical School.

“We can now begin to test preventative measures and treatments for depression and anxiety—some of which may be unique to females—and assess how they affect both behavior and neural activity in several of the networks that were most affected by social stress in this study,” Nephew concluded.

ABOUT THIS PSYCHOLOGY RESEARCH ARTICLE

Additional study authors are Wei Huang (currently at Massachusetts Institute of Technology), and Guillaume L. Poirier and Laurellee Payne, University of Massachusetts Medical School.

Funding: This work was supported by an award from the National Institute of Child Health and Human Development of the National Institutes of Health (HD059943) and a Brain and Behavior Research Foundation NARSAD Young Investigator Award to Nephew, as well as an award from the Office of the Director of the National Institutes of Health (OD018132-01) to the Center for Comparative NeuroImaging at University of Massachusetts Medical School.

Source: Tara Pettinato – Tufts University
Image Source: NeuroscienceNews.com image is credited to Marcelo Febo/University of Florida.
Original Research: Abstract for “A balance between elongation and trimming regulates telomere stability in stem cells” by Benjamin C. Nephew, Wei Huang, Guillaume L. Poirier, Laurellee Payne, and Jean A. King in Behavioural Brain Research. Published online December 2016 doi:10.1016/j.bbr.2016.08.051

CITE THIS NEUROSCIENCENEWS.COM ARTICLE
Tufts University “Early Life Social Stress Has Long Term Impact on Brain Networks: Rat Study.” NeuroscienceNews. NeuroscienceNews, 19 December 2016.
<http://neurosciencenews.com/social-stress-brain-network-5773/&gt;.

Abstract

A balance between elongation and trimming regulates telomere stability in stem cells

The use of a variety of neuroanatomical techniques has led to a greater understanding of the adverse effects of stress on psychiatric health. One recent advance that has been particularly valuable is the development of resting state functional connectivity (RSFC) in clinical studies. The current study investigates changes in RSFC in F1 adult female rats exposed to the early life chronic social stress (ECSS) of the daily introduction of a novel male intruder to the cage of their F0 mothers while the F1 pups are in the cage. This ECSS for the F1 animals consists of depressed maternal care from their F0 mothers and exposure to conflict between their F0 mothers and intruder males. Analyses of the functional connectivity data in ECSS exposed adult females versus control females reveal broad changes in the limbic and reward systems, the salience and introspective socioaffective networks, and several additional stress and social behavior associated nuclei. Substantial changes in connectivity were found in the prefrontal cortex, nucleus accumbens, hippocampus, and somatosensory cortex. The current rodent RSFC data support the hypothesis that the exposure to early life social stress has long term effects on neural connectivity in numerous social behavior, stress, and depression relevant brain nuclei. Future conscious rodent RSFC studies can build on the wealth of data generated from previous neuroanatomical studies of early life stress and enhance translational connectivity between animal and human fMRI studies in the development of novel preventative measures and treatments.

“A balance between elongation and trimming regulates telomere stability in stem cells” by Benjamin C. Nephew, Wei Huang, Guillaume L. Poirier, Laurellee Payne, and Jean A. King in Behavioural Brain Research. Published online December 2016 doi:10.1016/j.bbr.2016.08.051

A Molecular Link Between Type 2 Diabetes and Some Psychiatric Disorders

New research in The FASEB Journal suggests that prevalent protein found in schizophrenia also plays a direct role in the function of pancreatic beta cells, which produce insulin to maintain blood sugar levels.

There may be a genetic connection between some mental health disorders and type 2 diabetes. In a new report appearing in the February 2016 issue of The FASEB Journal, scientists show that a gene called “DISC1,” which is believed to play a role in mental health disorders, such as schizophrenia, bipolar disorder and some forms of depression, influences the function of pancreatic beta cells which produce insulin to maintain normal blood glucose levels.

“Studies exploring the biology of disease have increasingly identified the involvement of unanticipated proteins–DISC1 fits this category,” said Rita Bortell, Ph.D., a researcher involved in the work from the Diabetes Center of Excellence at the Universityof Massachusetts Medical School in Worcester, Massachusetts. “Our hope is that the association we’ve found linking disrupted DISC1 to both diabetes and psychiatric disorders may uncover mechanisms to improve therapies, even preventative ones, to alleviate suffering caused by both illnesses which are extraordinarily costly, very common, often quite debilitating.”

To make their discovery, Bortell and colleagues studied the function of DISC1 by comparing two groups of mice. The first group was genetically manipulated to disrupt the DISC1 gene only in the mouse’s pancreatic beta cells. The second group of mice was normal. The mice with disrupted DISC1 gene showed increased beta cell death, less insulin secretion and impaired glucose regulation while control mice were normal. The researchers found that DISC1 works by controlling the activity of a specific protein (GSK3β) already known to be critical for beta cell function and survival. Inhibition of GSK3β resulted in improved beta cell survival and restored normal glucose tolerance in mice with disrupted DISC1. Alterations in the DISC1 gene were originally associated with increased risk of schizophrenia, but further studies have also found DISC1 alterations in individuals with bipolar disorder and major depression.

Image shows a DNA double helix.

“The connections between these disorders may be surprising, but we have known for a long time that a single protein or gene can play multiple roles in the body,” said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal.

ABOUT THIS GENETICS RESEARCH

Source: Cody Mooneyhan – FASEB
Image Source: The image is in the public domain.
Original Research: Abstract for “Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β” by Agata Jurczyk, Anetta Nowosielska, Natalia Przewozniak, Ken-Edwin Aryee, Philip DiIorio, David Blodgett, Chaoxing Yang, Martha Campbell-Thompson, Mark Atkinson, Leonard Shultz, Ann Rittenhouse, David Harlan, Dale Greiner, and Rita Bortell in FASEB Journal. Published online February 2016 doi:10.1096/fj.15-279810


Abstract

Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β

Individuals with schizophrenia and their first-degree relatives have higher rates of type 2 diabetes (T2D) than the general population (18–30 vs. 1.2–6.3%), independent of body mass index and antipsychotic medication, suggesting shared genetic components may contribute to both diseases. The cause of this association remains unknown. Mutations in disrupted in schizophrenia 1 (DISC1) increase the risk of developing psychiatric disorders [logarithm (base 10) of odds = 7.1]. Here, we identified DISC1 as a major player controlling pancreatic β-cell proliferation and insulin secretion via regulation of glycogen synthase kinase-3β (GSK3β). DISC1 expression was enriched in developing mouse and human pancreas and adult β- and ductal cells. Loss of DISC1 function, through siRNA-mediated depletion or expression of a dominant-negative truncation that models the chromosomal translocation of human DISC1 in schizophrenia, resulted in decreased β-cell proliferation (3 vs. 1%; P < 0.01), increased apoptosis (0.1 vs. 0.6%; P < 0.01), and glucose intolerance in transgenic mice. Insulin secretion was reduced (0.5 vs. 0.1 ng/ml; P < 0.05), and critical β-cell transcription factors Pdx1 and Nkx6.1 were significantly decreased. Impaired DISC1 allowed inappropriate activation of GSK3β in β cells, and antagonizing GSK3β (SB216763; IC50 = 34.3 nM) rescued the β-cell defects. These results uncover an unexpected role for DISC1 in normal β-cell physiology and suggest that DISC1 dysregulation contributes to T2D independently of its importance for cognition.—Jurczyk, A., Nowosielska, A., Przewozniak, N., Aryee, K.-E., DiIorio, P., Blodgett, D., Yang, C., Campbell-Thompson, M., Atkinson, M., Shultz, L., Rittenhouse, A., Harlan, D., Greiner, D., Bortell, R. Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β.

“Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β” by Agata Jurczyk, Anetta Nowosielska, Natalia Przewozniak, Ken-Edwin Aryee, Philip DiIorio, David Blodgett, Chaoxing Yang, Martha Campbell-Thompson, Mark Atkinson, Leonard Shultz, Ann Rittenhouse, David Harlan, Dale Greiner, and Rita Bortell in FASEB Journal. Published online February 2016 doi:10.1096/fj.15-279810

Researchers Detail Link Between Stress and Diabetes

Summary: Researchers report they have established a link between emotional stress and diabetes.

Source: Rice University.

Connection established between anxiety control, inflammation and Type 2 diabetes.

A Rice University study has found a link between emotional stress and diabetes, with roots in the brain’s ability to control anxiety.

That control lies with the brain’s executive functions, processes that handle attention, inhibition, working memory and cognitive flexibility and are also involved in reasoning, problem-solving and planning.

The study published in Psychoneuroendocrinology establishes a metabolic chain reaction that starts with low inhibition, aka attention control, which leaves a person vulnerable to tempting or distracting information, objects, thoughts or activities. Previous studies have shown that such vulnerability can lead to more frequent anxiety, and anxiety is known to activate a metabolic pathway responsible for the production of pro-inflammatory cytokines, signaling proteins that include interleukin-6 (IL-6).

Flow chart extablishes the link between stress and diabetes.

Along with cognitive tests that measured attention control, the Rice study measured levels of both blood glucose and IL-6 in more than 800 adults. IL-6 is a protein the body produces to stimulate immune response and healing. It is a biomarker of acute and chronic stress that also has been associated with a greater likelihood of diabetes and high blood glucose.

The research showed individuals with low inhibition were more likely to have diabetes than those with high inhibition due to the pathway from high anxiety to IL-6. The results were the same no matter how subjects performed on other cognitive tests, like those for memory and problem-solving.

Researchers have suspected a link between anxiety and poor health, including diabetes, for many years but none have detailed the biological pathway responsible, said lead author Kyle Murdock, a postdoctoral research fellow in psychology. He said the Rice study takes a deeper look at how inflammation bridges the two.

“The literature shows individuals with poor inhibition are more likely to experience stressful thoughts and have a harder time breaking their attention away from them,” Murdock said. “That made me wonder if there’s a stress-induced pathway that could link inhibition with inflammation and the diseases we’re interested in, such as diabetes.

“Plenty of research shows that when individuals are stressed or anxious or depressed, inflammation goes up,” he said. “The novel part of our study was establishing the pathway from inhibition to anxiety to inflammation to diabetes.”

Murdock works in the Rice lab of Christopher Fagundes, assistant professor of psychology. The Fagundes lab investigates processes that happen along the border of psychology and physiology, and how those processes affect overall health and potential treatments.

The data came from a Midlife Development in the United States study of 1,255 middle-aged adults whose cognitive abilities were tested two years apart. More than 800 of those also underwent blood tests to check IL-6 and glucose levels. The Rice researchers found not only the positive link between inhibition and diabetes, but the absence of a link between other cognitive functions and the disease. They also determined that the pathway only went in one direction: Inflammation never appeared to affect inhibition. Murdock said a year as a clinical psychology intern at the Oregon Health and Science University, where he studied with co-author and psychologist Danny Duke, led the researchers to think there could also be a feedback loop at play in those with diabetes. “Individuals who are anxious are more likely to avoid treatment and use maladaptive strategies (like smoking or unhealthy diets) that enhance their blood glucose, which is problematic. It’s a snowball effect: The further they go, the worse it gets,” he said.

“We also know that extremely high blood glucose can impact cognition as well. We talked about how, if we’re going to treat these individuals appropriately, it won’t be by sitting them down in a room and saying, ‘Hey, you need to eat better,’ or ‘You need to use your insulin on time.’”

The researchers listed several possible interventions, including mindfulness therapy, stimulant or anti-inflammatory medications and cognitive behavioral therapy. “Research shows that people who practice mindfulness do better on the inhibition tests over time,” Murdock said, suggesting that shifting one’s attention away from stressful thoughts may affect physiological responses.

“I’m a firm believer that mindfulness-based approaches to treatment are a great idea, for a lot of reasons,” Fagundes said. “That doesn’t mean medicines that promote inhibition, such as stimulants, shouldn’t be considered, but a combination of the two could be really helpful.”

ABOUT THIS PSYCHOLOGY RESEARCH ARTICLE

Co-authors of the paper are Angie LeRoy, a Rice staff member and a graduate student at the University of Houston; and Tamara Lacourt, a postdoctoral researcher, and Cobi Heijnen, a professor of symptom research at the University of Texas MD Anderson Cancer Center.

Funding: The National Institute on Aging and the National Heart, Lung and Blood Institute supported the research.

Source: Jeff Falk – Rice University
Image Source: This NeuroscienceNews.com image is credited to Andrea Lugo/Rice University.
Original Research Abstract “Executive functioning and diabetes: The role of anxious arousal and inflammation” by Kyle W. Murdock, Angie S. LeRoy, Tamara E. Lacourt, Danny C. Duke, Cobi J. Heijnen, and Christopher P. Fagundes in Psychoneuroendocrinology. Published online May 18 2016 doi:10.1016/j.psyneuen.2016.05.006

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Abstract

Executive functioning and diabetes: The role of anxious arousal and inflammation

Individuals who perform poorly on measures of the executive function of inhibition have higher anxious arousal in comparison to those with better performance. High anxious arousal is associated with a pro-inflammatory response. Chronically high anxious arousal and inflammation increase one’s risk of developing type 2 diabetes. We sought to evaluate anxious arousal and inflammation as underlying mechanisms linking inhibition with diabetes incidence. Participants (N = 835) completed measures of cognitive abilities, a self-report measure of anxious arousal, and donated blood to assess interleukin-6 (IL-6) and glycated hemoglobin (HbA1c). Individuals with low inhibition were more likely to have diabetes than those with high inhibition due to the serial pathway from high anxious arousal to IL-6. Findings remained when entering other indicators of cognitive abilities as covariates, suggesting that inhibition is a unique cognitive ability associated with diabetes incidence. On the basis of our results, we propose several avenues to explore for improved prevention and treatment efforts for type 2 diabetes.

“Executive functioning and diabetes: The role of anxious arousal and inflammation” by Kyle W. Murdock, Angie S. LeRoy, Tamara E. Lacourt, Danny C. Duke, Cobi J. Heijnen, and Christopher P. Fagundes in Psychoneuroendocrinology. Published online May 18 2016 doi:10.1016/j.psyneuen.2016.05.006