Nagoya University Graduate School of Medicine
You are about to take the stage to speak in front of a large audience. As you wait, your heart starts to pound, your breathing quickens, your blood pressure rises and your palms sweat. These physiological responses are evolutionarily conserved mechanisms to prepare your body to fight against imminent dangers, or to run away quickly. Another key response is an increase in body temperature. Emotional stress can cause this psychogenic fever in many mammalian species, from rodents to humans1,2. What is the neural mechanism that underlies this phenomenon? Writing in Science, Kataoka et al.3 describe a key neural circuit in psychologically induced hyperthermia.
The current work builds on a long legacy of research by the same group, who began their quest for a neuronal circuit that triggers heat production in 2004, using brown fat tissue as an entry point4. Brown fat is a type of ‘good’ fat that can generate heat when needed. Blocking the activity of β3-adrenergic receptor proteins, which are abundant in brown fat and enable the tissue to respond to signals from neurons, attenuates stress-induced hyperthermia5.
In the 2004 study, the researchers injected viral ‘retrograde tracers’ into brown fat in rats; the tracers move through connected neurons, allowing the authors to identify brain regions from which neurons project to the fat4. This revealed that neurons in a brainstem area called the rostral medullary raphe (rMR) connect to brown fat. Later on, the same group identified2 the dorsomedial hypothalamus (DMH) as a key brain region upstream of the rMR. When the authors artificially activated the DMH-to-rMR pathway, they found an increase in neuronal activity and heat production in brown fat. Unexpectedly, activating this pathway also increased heart rate and blood pressure, suggesting that DMH–rMR could coordinate various physiological responses during stress.
In humans, psychological stress often involves an understanding of complicated situations, and thus probably requires instructions from regions of the brain’s cortex, which is involved in cognition. In the current study, Kataoka et al. set out to identify the cortical regions that could send these instructions to the DMH. As in their previous work, the authors used retrograde tracers — this time, injected into the DMH — to look for neurons that link into their heat-generating circuit. They found that only one, little-studied, region of the cortex was strongly labelled by the tracer. This region, called the dorsal peduncular cortex and dorsal taenia tecta (DP/DTT), is also highly active in rats in the wake of social defeat (a hostile interaction in which the animal has lost a fight with another, dominant rat).
To examine the role of this region in stress responses, the authors impaired its connection to the DMH in three ways. They blocked activity throughout the DP/DTT using a chemical inhibitor; they used a virus to kill cells projecting from the DP/DTT to the DMH; and they used a sophisticated genetic approach to inhibit activity specifically in the projections that DP/DTT neurons send to the DMH. In each case, their intervention reduced stress-induced hyperthermia.
By contrast, artificial activation of the neuronal projections between the two regions elicited a battery of responses, including increases in heart rate, blood pressure, and heat production in brown fat. The group provided evidence that the DP/DTT neurons send excitatory signals to the DMH, and demonstrated that the projections from the DP/DTT terminate close to the DMH cells that, in turn, project to the rMR. Taken together, Kataoka and colleagues’ experiments support the idea of a DP/DTT–DMH–rMR–brown fat circuit for heat production in response to stress
How does the stress-related information reach the DP/DTT? Further retrograde tracing experiments revealed that the strongest inputs to the DP/DTT are from the brain’s midline thalamic regions, including the paraventricular (PVT) and mediodorsal (MD) thalamic nuclei. The PVT is highly sensitive to various physical and psychological stressors, such as predator cues and pain6. By contrast, the MD interacts with the prefrontal cortex to mediate complex cognitive functions, such as rule learning, abstraction, evaluation and (in humans) imagination7. Thus, every possible stressor, from physical pain to anticipated legal trouble, can find their way to the DP/DTT. It remains unclear, however, how different stressors are encoded in the DP/DTT, whether the responses of the DP/DTT to stressors are influenced by experience, and whether deficits in DP/DTT cells could be responsible for abnormal physiological responses to stress. Future studies using electrophysiological or optical recordings of the DP/DTT cells will help to address these questions.
The philosopher and psychologist William James suggested that fear is an interpretation of physiological responses to threat, instead of the other way around8. In other words, rather than running from a bear because we are afraid, we are afraid because we are running from a bear. If James is right, rats should stop being afraid if their physiological responses to a threat are blocked. Kataoka et al. therefore asked whether inhibiting the DP/DTT–DMH pathway can suppress the fear that a rat shows when presented with an aggressive, dominant counterpart that has recently defeated it in a stressful social interaction.
Under normal conditions, a defeated animal will try to stay away from the aggressor to avoid incurring further damage. By contrast, naive animals that have not previously gone through a social defeat show no signs of fear, and investigate the dominant rat with great interest. Remarkably, when the authors blocked the DP/DTT–DMH pathway in rats that had been defeated, the animals behaved like naive rats.
Thus, the behavioural manifestation of fear, and perhaps the perception of fear (which can only be inferred from behaviours in rats), depends on bodily responses to threat. These data provide an indication of why taking a deep breath before that big public speech might help to calm us down. The data also suggest that suppressing physiological responses to stress could be an effective way to alleviate stressful feelings. Of importance in this context, non-stress-related thermoregulation — changes in internal temperature caused by infections or external temperature change, for instance — is mediated, not by the DP/DTT, but by another region upstream of the DMH, the preoptic area9. Blocking the DP/DTT–DMH pathway would therefore be expected to leave day-to-day regulation of temperature unchanged. It is early days, but manipulation of the DP/DTT could potentially be a way to curb chronic psychological stress.
Protective effects of curcumin against neuroinflammation
Wenzhou Medical University (China), April 1, 2020
According to news reporting originating from Wenzhou, People’s Republic of China, he research stated, “Activated microglia induced by amyloid-beta (A beta) release proinflammatory cytokines that can induce neurotoxicity. High-mobility group box I protein (HMGB1) and HMGB1-mediated inflammatory responses have been attributed with memory impairment in patients with Alzheimer’s disease (AD).”
Our news editors obtained a quote from the research from Wenzhou Medical University, “There is accumulating evidence to suggest curcumin is a potent anti-inflammatory polyphenol. However, whether curcumin could effectively inhibit inflammation through the suppression of HMGB1 production or HMGB1-mediated inflammatory responses in AP-activated microglia is still unclear. Primary microglia were prepared from the cerebral cortices of one- to three-day-old Sprague Dawley rats. The microglia were cultured and treated with A beta(25-35) 50 mu M for 24 h to prove a toxic effect. Curcumin 10 mu M was administrated 1 h before A beta(25-45) treatment. The levels of HMGB1, interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) in the culture medium were analyzed by ELISA. Western blotting was conducted to assess the expression level of toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, PC12 cells were treated with conditioned medium from microglia treated with A beta(25-35), or A beta(25-35) and curcumin, and cell viability was subsequently assessed by MTT. Curcumin was found to significantly inhibit HMGB1 expression and release in A beta(25-35)-stimulated microglia. Pretreatment with curcumin reduced TLR4 and RAGE expression. Proinflammatory cytokines such as IL-1 beta and TNF-alpha were also remarkably reduced by curcumin. In addition, curcumin protected neurons from indirect toxicity mediated by A beta(25-35)-treated microglia.”
According to the news editors, the research concluded: “Curcumin effectively inhibits A beta(25-35)-induced neuroinflammation in microglia, partly by suppressing the expression of HMGB1, TLR4, and RAGE.”
Making healthy lifestyle choices can prevent the onset of dementia
Universities of Exeter, Michigan, Oxford and Southern Australia, April 2, 2020
Researchers found that individuals aged 60 years and above who follow a healthy lifestyle have a lower risk of dementia than those who have an unhealthy lifestyle. Additionally, they found that genetic risk can be mitigated by healthy lifestyle choices.
The study was a collaboration between researchers from the University of Exeter in the U.K., the University of Michigan, the University of Oxford and the University of South Australia.
Fortunately, the onset of dementia can be prevented. In their study, American and British researchers hypothesized that adherence to a healthy lifestyle can greatly reduce the risk of dementia.
To test this hypothesis, the researchers examined data drawn from the UK Biobank, a prospective cohort study that collected data from approximately 500,000 individuals in the U.K. from 2006 to 2010. The researchers restricted their analyses to data from individuals aged 60 years and above, who had no symptoms or diagnosis of dementia. The number of participants that fit the criteria amounted to 196,383.
To assess the participants’ lifestyles, the researchers used a touchscreen questionnaire that scored the participants based on the following dementia risk factors: smoking status, physical activity, diet and alcohol consumption.
Over a follow-up period of eight years, the researchers identified 1,769 cases of dementia. Surprisingly, they found that participants with unhealthy lifestyles, regardless of their genetic risk, had a higher likelihood of developing dementia than participants who followed healthier lifestyles.
This suggests that a person’s lifestyle choices can dictate his dementia risk, regardless of whether he is genetically predisposed to dementia or not. Having a healthy lifestyle can help prevent a person from developing dementia.
Dementia is the leading cause of disability and dependency among older individuals. Fortunately, the study proved that dementia is not inevitable. According to David Llewellyn, one of the authors of the study, their research “delivers a really important message that undermines a fatalistic view of dementia.”
Ever wonder why you sometimes get cravings after seeing a picture of food, even though you know you aren’t really hungry? According to a recent study, it’s all in the mind, or more precisely, in how the mind processes food cues.
According to psychologists at Dartmouth College, there is a physiological process responsible for heightened sensitivity to food cues that brings about food cravings. Using functional magnetic resonance imaging (fMRI), the researchers were able to observe changes in the brain when volunteers were exposed to images of food.
The data comes as part of a study focused on figuring out how exposure to certain kinds of images can help predict behavior. The idea that the researchers wanted to demonstrate was that exposure to such images can lead to failures in self-regulation.
The brain gives you food cravings when it sees food cues
To test their hypothesis, the scientists had female college students weighed and had their brains scanned using fMRI while viewing images of neutral scenes and appetizing foods. The fMRI scans focused on changes to the nucleus accumbens of the volunteers.
Located deep near the basal region of the brain, the nucleus accumbens is part of its reward system. Specifically, it controls the reward and punishment centers of the brain, transferring relevant motivational information to the motor cells in order to obtain a certain reward or satisfaction. This, of course, includes the satisfaction felt when eating.
Based on this, the researchers theorized that there is a relationship between greater activity in the nucleus accumbens while viewing pictures of food and weight gain. Any participants who showed less response to the images would be less likely to gain weight.
Six months after the scans, the participants returned to the lab for a follow-up weighing. As expected, those who demonstrated greater activity in the nucleus accumbens when viewing food images did actually gain weight.
Exposure can occur unconsciously
The interesting, but also frightening, thing that the study discovered was that the whole process can take place unconsciously. Just seeing triggers on TV commercials or other media can increase the likelihood of cravings and eating. In a way, the study sheds new light on just how effective the food-related imagery in such commercials can be. (Related: Fighting your cravings: Researchers identify new brain circuits that can help curb junk food cravings.)
The study also demonstrates how resisting cravings triggered by these images and commercials isn’t just a matter of “will power” — there are actual physiological processes driving them. Learning about how these images can cause cravings can go a long way towards resisting them.
More than just food cravings
The study is just one part of a larger study on how images, in general, can affect the nucleus accumbens and predict behavior. In addition to food, the researchers also studied reactions towards sexually suggestive images and whether or not it resulted in an increase in sexual activity.
Upon returning after six months, the participants were also made to answer two surveys for sexual activity, the Sociosexual Orientation Inventory and the Sexual Desire Inventory (SDI). The researchers noted a correlation between increased activity in the nucleus accumbens when viewing sexually suggestive images and sexual activity (both alone and with a partner).
Based on these results, scientists believe that further research into how the nucleus accumbens and the brain’s reward centers react to images could be useful for predicting health risks, such as obesity and sexually transmitted diseases (STD). It can also give further insight into how such imagery can be used and abused by certain parties, such as advertisers, to their benefit and the public’s detriment.
Older people generally more emotionally healthy, better able to resist daily temptations
Duke University, March 24, 2020
The stereotype of grumpy old people apparently doesn't hold up under closer inspection. A new study from Duke and Vanderbilt University psychologists finds that older people are generally more emotionally stable and better able to resist temptations in their daily lives.
"There is evidence here that emotional health and regulation improve with age," said Daisy Burr, a Duke PhD student who led the study with Gregory Samanez-Larkin, an assistant professor of psychology and neuroscience. Their work appeared March 23 in the journal Emotion.
The researchers pinged 123 study participants aged 20 to 80 on their cell phones three times a day for ten days. Participants were asked to indicate how they felt on a five-point scale for each of eight emotional states, including contentment, enthusiasm, relaxation and sluggishness. Then they were asked whether they were desiring anything right then, including food or alcohol, cigarettes, social media, shopping, talking to someone, sex, sleep or work. They could report up to three temptations at once.
Each participant had also been assessed on a standard measure of "global life satisfaction," which determined their general well-being, regardless of the moment-to-moment moods.
What the researchers were looking for is how positive or negative feelings and the ability to resist temptations might change as people get older.
What they found is that the older people in the study were more stable and "less volatile in their emotions," Samanez-Larkin said. And age, it turns out, is a stronger predictor of the ability to resist temptation than the emotional state.
Samenez-Larkin said a person's goals change with age. The older person may be more oriented toward the present and "trying to maximize well-being every day. You want to feel good as much as possible."
The researchers said their findings are a better reflection of real-world conditions because they surveyed participants in their own time and space, rather than having them respond to cues in a laboratory setting. Burr added that older people are better at regulating their emotional state when allowed to do what they want.
In the end, Burr's analysis of the data found people experiencing more negative affect are worse at resisting desires. Younger study participants who had higher levels of life satisfaction were better able to resist desires.
But older adults were better at resisting temptation, regardless of their life satisfaction.
Most diets lead to weight loss and lower blood pressure, but effects largely disappear after a year
Monash University (Australia), April 1, 2020
Reasonably good evidence suggests that most diets result in similar modest weight loss and improvements in cardiovascular risk factors over a period of six months, compared with a usual diet, finds a study published by The BMJ today.
Weight reduction at the 12 month follow-up diminished, and improvements in cardiovascular risk factors largely disappeared, except in association with the Mediterranean diet, which saw a small but important reduction in 'bad' LDL cholesterol.
As such, at least for short-term benefits, the researchers suggest that people should choose the diet they prefer without concern about the size of benefits.
Obesity has nearly tripled worldwide since 1975, prompting a plethora of dietary recommendations for weight management and cardiovascular risk reduction.
But so far, there has been no comprehensive analysis comparing the relative impact of different diets for weight loss and improving cardiovascular risk factors, such as blood pressure and cholesterol levels.
To address this, a team of international researchers set out to determine the relative effectiveness of dietary patterns and popular named diets among overweight or obese adults.
Their findings are based on the results of 121 randomised trials with 21,942 patients (average age 49) who followed a popular named diet or an alternative control diet and reported weight loss, and changes in cardiovascular risk factors.
The studies were designed differently, and were of varying quality, but the researchers were able to allow for that in their analysis.
They grouped diets by macronutrient patterns (low carbohydrate, low fat, and moderate macronutrient—similar to low fat, but slightly more fat and slightly less carbohydrate) and according to 14 popular named dietary programmes (Atkins, DASH, Mediteranean, etc).
Compared with a usual diet, low carbohydrate and low fat diets resulted in a similar modest reduction in weight (between 4 and 5 kg) and reductions in blood pressure at six months. Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions.
Among popular named diets, Atkins, DASH, and Zone had the largest effect on weight loss (between 3.5 and 5.5 kg) and blood pressure compared with a usual diet at six months. No diets significantly improved levels of 'good' HDL cholesterol or C reactive protein (a chemical associated with inflammation) at six months.
Overall, weight loss diminished at 12 months among all dietary patterns and popular named diets, while the benefits for cardiovascular risk factors of all diets, except the Mediterranean diet, essentially disappeared.
The researchers point to some study limitations that could have affected the accuracy of their estimates. But say their comprehensive search and thorough analyses supports the robustness of the results.
As such, they say moderate certainty evidence shows that most macronutrient diets result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure, at six but not 12 months.
Differences between diets are, however, generally trivial to small, implying that for short-term cardiovascular benefit people can choose the diet they prefer from among many of the available diets without concern about the magnitude of benefits, they conclude.
The extensive range of popular diets analysed "provides a plethora of choice but no clear winner," say researchers at Monash University, Australia in a linked editorial.
As such, they suggest conversations should shift away from specific choice of diet, and focus instead on how best to maintain any weight loss achieved.
As national dietary guidelines fail to resonate with the public, taking a food-based approach with individuals and encouraging them to eat more vegetables, legumes, and whole grains and less sugar, salt and alcohol is sound advice, they add.
"If we are to change the weight trajectory of whole populations, we may learn more from understanding how commercial diet companies engage and retain their customers, and translate that knowledge into more effective health promotion campaigns," they conclude.
Dietary niacin intake affects risk of hip fracture, hip bone mineral density
Medical College of Georgia and University of Washington, April 2, 2020
Niacin, also known as vitamin B3, is an essential micronutrient that helps the body break down carbohydrates, fats and proteins and convert them into energy. It is also involved in the production of certain hormones and plays a role in liver function. Niacin can be obtained from a wide variety of food sources, such as organ meats like liver, white meat and fish.
However, recent studies suggest that niacin intake may have an influence on the development of age-related diseases. To investigate this, researchers from different universities in the U.S. examined the association of dietary niacin intake with multiple skeletal health parameters, such as bone mineral density (BMD), hip fractures and body composition.
In their paper, which appeared in the Journal of Bone and Mineral Research, they detailed how consuming too much or too little of this important vitamin can affect bone health, particularly in the elderly.
Low or high intake of niacin can increase the risk of hip fractures in older adults
According to the researchers, interest in niacin has increased recently due to its potential involvement in diseases associated with aging. However, to date, no study has investigated its influence on bone health, particularly in African American and white men and women.
For their study, the researchers recruited 5,187 men and women from the Cardiovascular Health Study (CHS), a population-based study of coronary heart disease and stroke in adults aged 65 and above. These participants have a mean daily dietary niacin intake of 32.6 milligrams (mg) and were divided into four groups:
- Group 1, with an intake of 3.6 to 21.8 mg per day
- Group 2, with an intake of 21.9 to 30.2 mg per day
- Group 3, with an intake of 30.3 to 40.9 mg per day
- Group 4, with an intake of 41 to 102.4 mg per day
The researchers estimated the risk of incident hip fracture per 10 mg increment of daily dietary niacin intake using proportional hazards models.
They reported that during a median follow-up of 13 years, 725 participants had an incident hip fracture. Adjusting for demographic, clinical characteristics and diet, the researchers found that high and low dietary niacin intake was significantly associated with an increased risk of hip fractures.
The two groups with the lowest and highest niacin intake had an increased risk of incident hip fracture compared with groups 2 and 3. Meanwhile, dietary niacin intake was inversely associated with hip BMD. However, it had no significant association with total body BMD or any body composition measures.
Based on these findings, the researchers concluded that in elderly, community-dwelling African American and white men and women, high and low dietary niacin intake significantly increases the risk of hip fracture.
Teen marijuana use boosts risk of adult insomnia
University of Colorado, April 1, 2020
Smoke a lot of weed as a teenager, and when you reach adulthood you'll be more likely to have trouble falling or staying asleep, according to a new University of Colorado Boulder study of nearly 2,000 twins.
The study, published in the journal Sleep, comes at a time when cannabis—in everything from THC-infused gummies to prerolled joints and high-potency vape pens—is increasingly being marketed as a sleep aid in states where marijuana is legal. It adds to a growing body of evidence suggesting that while it may help some users fall asleep occasionally, chronic use can have negative long-term consequences, particularly for the young.
"People tend to think that cannabis helps with sleep, but if you look closely at the studies, continued or excessive use is also associated with a lot of sleep deficits," said lead author Evan Winiger, a graduate student in the Institute for Behavioral Genetics. "Our study adds to that literature, showing for the first time that early use is associated with increased rates of insomnia later on."
For the study, Winiger analyzed data from 1,882 young adults from the Colorado Twin Registry, which has been following twins for research since 1968. Each had completed surveys about their sleep habits, marijuana use and mental health.
They found that about one-third of subjects who started using marijuana regularly before age 18 had insomnia in adulthood, compared to less than 20% among those who didn't use cannabis regularly as teens. The same pattern held true for a particularly hazardous form of insomnia known as "short sleep" (sleeping fewer than six hours per night on a regular basis). About one in 10 subjects who used cannabis regularly as teens grew up to be short-sleepers, while only about 5% of non-users did.
People who started using marijuana after they turned 18 also had slightly higher rates of insomnia in young adulthood. And these patterns persisted when controlling for depression, anxiety and shift work (which can all also impair sleep).
Lasting impacts on developing brains
Exactly why early cannabis use correlates with later sleep problems remains unclear, but several theories are emerging.
As Winiger explains, the human body has its own endocannabinoid system, producing chemicals much like the cannabinoids (CBD and THC) present in marijuana that bind to cannabinoid receptors in our brains and have been shown to influence our cognition, emotions and circadian rhythm—or body clock.
"One theory is that these receptors are being desensitized or disturbed from all the cannabis use at a time that the brain is still developing, and that leads to waking issues later," he said.
It could also be that cannabis use in adolescence leads to structural changes in the brain. (Previous brain imaging studies have shown it can alter the developing prefrontal cortex.)
Or chronic use may set teens up for poor sleep habits when they are young, which linger into adulthood.
Genes may also be at play.
By looking at 472 identical twin pairs (who share 100% of their genetic makeup) and 304 fraternal pairs (who share only 50%), the researchers were able to infer to what degree the traits were inherited. They concluded that many of the same genes that contribute to the risk of early cannabis use are also associated with insomnia and insomnia with short sleep.
This is the first study to find a direct genetic correlation between cannabis use and insomnia.
In short, it remains a chicken-and-egg question.
"It is possible that sleep problems could influence cannabis use, cannabis use could influence sleep problems, or common genetics could be responsible," the authors wrote.
Co-author Ken Wright, director of the Sleep and Chronobiology lab, says the study does not necessarily mean all strains of marijuana are bad for sleep in all people all the time. Some previous studies show cannabis can help people fall asleep if used occasionally.
"The evidence in adults is quite mixed, and unfortunately we can't do randomized controlled trials with different strains and different doses," Wright said, pointing to federal laws that prohibit researchers from handling cannabis, providing it to subjects or being present while subjects use it.
What he can say now is this:
"We would not recommend that teenagers utilize marijuana to promote their sleep. Anytime you are dealing with a developing brain you need to be cautious."
