hypothalamus,

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How Stress Affects the Brain

Are you sleeping restlessly, feeling irritable or moody, forgetting little things, and feeling overwhelmed and isolated? Don’t worry. We’ve all been there. You’re probably just stressed out. Stress isn’t always a bad thing. It can be handy for a burst of extra energy and focus, like when you’re playing a competitive sport, or have to speak in public. But when its continuous, the kind most of us face day in and day out, it actually begins to change your brain. Chronic stress, like being overworked or having arguments at home, can affect brain size, its structure, and how it functions, right down to the level of your genes.

Stress begins with something called the hypothalamus pituitary adrenal axis, series of interactions between endocrine glands in the brain and on the kidney, which controls your body’s reaction to stress. When your brain detects a stressful situation, your HPA axis is instantly activated and releases a hormone called cortisol, which primes your body for instant action. But high levels of cortisol over long periods of time wreak havoc on your brain. For example, chronic stress increases the activity level and number of neural connections in the amygdala, your brain’s fear center. And as levels of cortisol rise, electric signals in your hippocampus, the part of the brain associated with learning, memories, and stress control, deteriorate.

The hippocampus also inhibits the activity of the HPA axis, so when it weakens, so does your ability to control your stress. That’s not all, though. Cortisol can literally cause your brain to shrink in size.

Too much of it results in the loss of synaptic connections between neurons and the shrinking of your prefrontal cortex, the part of your brain the regulates behaviors like concentration, decision-making, judgement, and social interaction. It also leads to fewer new brain cells being made in the hippocampus. This means chronic stress might make it harder for you to learn and remember things, and also set the stage for more serious mental problems, like depression and eventually Alzheimer’s disease.

It’s not all bad news, though. There are many ways to reverse what cortisol does to your stressed brain. The most powerful weapons are exercise and meditation, which involves breathing deeply and being aware and focused on your surroundings. Both of these activities decrease your stress and increase the size of the hippocampus, thereby improving your memory.

So don’t feel defeated by the pressures of daily life. Get in control of your stress before it takes control of you.

Source: TED-Ed Lesson How stress affects your brain - Madhumita Murgia

Animation by Andrew Zimbelman

The brain’s reaction to male odor shifts at puberty in children with gender dysphoria

The brains of children with gender dysphoria react to androstadienone, a musky-smelling steroid produced by men, in a way typical of their biological sex, but after puberty according to their experienced gender, finds a study for the first time in the open-access journal Frontiers in Endocrinology.

Around puberty, the testes of men start to produce androstadienone, a breakdown product of testosterone. Men release it in their sweat, especially from the armpits. Its only known function is to work like a pheromone: when women smell androstadienone, their mood tends to improve, their blood pressure, heart rate, and breathing go up, and they may become aroused.

Previous studies have shown that, in heterosexual women, the brain region that responds most to androstadienone is the hypothalamus, which lies just above the brainstem and links the nervous system to the hormonal system. In men with gender dysphoria (formerly called gender identity disorder) – who are born as males, but behave as and identify with women, and want to change sex – the hypothalamus also reacts strongly to its odor. In contrast, the hypothalamus of heterosexual men hardly responds to it.

Girls without gender dysphoria before puberty already show a stronger reaction in the hypothalamus to androstadienone than boys, finds a new study by Sarah Burke and colleagues from the VU University Medical Center of Amsterdam, the Netherlands, and the University of Liège, Belgium.

The researchers used neuroimaging to also show for the first time that in prepubescent children with gender dysphoria, the hypothalamus reacts to the smell of androstadienone in a way typical of their biological sex. Around puberty, its response shifts, and becomes typical of their experienced gender.

The reaction to the smell of androstadienone in the hypothalamus of 154 children and adolescents, including girls and boys, both before (7 to 11-year-old) and after puberty (15 to 16-year-old), of whom 74 had been diagnosed with gender dysphoria.

Results showed that the hypothalamus was more responsive to androstadienone in 7 to 11-year-old girls than in boys, both without gender dysphoria, although not yet as much as in adolescent girls. This means that the greater receptiveness of women to its odor already exists before puberty, either as an inborn difference or one that arises during early childhood.

Before puberty, the hypothalamus of boys with gender dysphoria hardly reacted to the odor, just as in other boys. But this changed in the 15 to 16-year-olds: the hypothalamus of adolescent boys with gender dysphoria now lit up as much as in heterosexual women, while the other adolescent boys still did not show any reaction. Adolescent girls with gender dysphoria showed the same reaction to androstadienone in their hypothalamus as is typical for heterosexual men.

These results suggest that as children with gender dysphoria grow up, their brain naturally undergoes a partial rewiring, to become more similar to the brain of the opposite sex – so corresponding to their experienced gender.

Deep within the brain’s hypothalamus, there is a collection of neurons that serve as the central regulators of appetite, metabolism and fat storage. Called the arcuate nucleus, these neurons respond to circulating hunger and satiety signals in blood, increasing or decreasing our food intake accordingly.

It’s no wonder then, that the arcuate nucleus is one of the main focus areas when looking into the neurological influences of obesity. In a recent study, researchers at Children’s Hospital Los Angeles (CHLA) found that the presence of the “hunger hormone” ghrelin—which initiates our urge to eat—in early infancy can cause changes to the arcuate nucleus that may link to an increased risk of obesity later in life.

Read more about how ghrelin levels affect the brain and influence obesity risk

Image Caption: Immunofluorescent staining of neuronal culture derived from the arcuate nucleus

Image Credit: Richard Simerly, PhD, director of the Developmental Neuroscience Program and deputy director of The Saban Research Institute of CHLA

Can ‘love hormone’ protect against addiction?

Researchers at the University of Adelaide say addictive behaviour such as drug and alcohol abuse could be associated with poor development of the so-called “love hormone” system in our bodies during early childhood.

The groundbreaking idea has resulted from a review of worldwide research into oxytocin, known as the “love hormone” or “bonding drug” because of its important role in enhancing social interactions, maternal behaviour and partnership.

This month’s special edition of the international journal Pharmacology, Biochemistry and Behavior deals with the current state of research linking oxytocin and addiction, and has been guest edited by Dr Femke Buisman-Pijlman from the University of Adelaide’s School of Medical Sciences.

Dr Buisman-Pijlman, who has a background in both addiction studies and family studies, says some people’s lack of resilience to addictive behaviours may be linked to poor development of their oxytocin systems.

“We know that newborn babies already have levels of oxytocin in their bodies, and this helps to create the all-important bond between a mother and her child. But our oxytocin systems aren’t fully developed when we’re born - they don’t finish developing until the age of three, which means our systems are potentially subject to a range of influences both external and internal,” Dr Buisman-Pijlman says.

She says the oxytocin system develops mainly based on experiences.

“The main factors that affect our oxytocin systems are genetics, gender and environment. You can’t change the genes you’re born with, but environmental factors play a substantial role in the development of the oxytocin system until our systems are fully developed,” Dr Buisman-Pijlman says.

“Previous research has shown that there is a high degree of variability in people’s oxytocin levels. We’re interested in how and why people have such differences in oxytocin, and what we can do about it to have a beneficial impact on people’s health and wellbeing,” she says.

She says studies show that some risk factors for drug addiction already exist at four years of age. “And because the hardware of the oxytocin system finishes developing in our bodies at around age three, this could be a critical window to study. Oxytocin can reduce the pleasure of drugs and feeling of stress, but only if the system develops well.”

Her theory is that adversity in early life is key to the impaired development of the oxytocin system. “This adversity could take the form of a difficult birth, disturbed bonding or abuse, deprivation, or severe infection, to name just a few factors,” Dr Buisman-Pijlman says.

“Understanding what occurs with the oxytocin system during the first few years of life could help us to unravel this aspect of addictive behaviour and use that knowledge for treatment and prevention.”

When temperatures are cool and food is scarce, the western pygmy possum will enter a mini-hibernation called a torpor. Similar to humans, the western pygmy possum experiences REM (rapid eye movement) sleep. During this stage, they go into a dream state where they dream of eating food–satisfying the hypothalamus, which is the area of the brain responsible for signalling hunger. 

How Stress Affects the Brain

Are you sleeping restlessly, feeling irritable or moody, forgetting little things, and feeling overwhelmed and isolated? Don’t worry. We’ve all been there. You’re probably just stressed out. Stress isn’t always a bad thing. It can be handy for a burst of extra energy and focus, like when you’re playing a competitive sport, or have to speak in public. But when its continuous, the kind most of us face day in and day out, it actually begins to change your brain. Chronic stress, like being overworked or having arguments at home, can affect brain size, its structure, and how it functions, right down to the level of your genes.

Stress begins with something called the hypothalamus pituitary adrenal axis, series of interactions between endocrine glands in the brain and on the kidney, which controls your body’s reaction to stress. When your brain detects a stressful situation, your HPA axis is instantly activated and releases a hormone called cortisol, which primes your body for instant action. But high levels of cortisol over long periods of time wreak havoc on your brain. For example, chronic stress increases the activity level and number of neural connections in the amygdala, your brain’s fear center. And as levels of cortisol rise, electric signals in your hippocampus, the part of the brain associated with learning, memories, and stress control, deteriorate.

The hippocampus also inhibits the activity of the HPA axis, so when it weakens, so does your ability to control your stress. That’s not all, though. Cortisol can literally cause your brain to shrink in size.

Too much of it results in the loss of synaptic connections between neurons and the shrinking of your prefrontal cortex, the part of your brain the regulates behaviors like concentration, decision-making, judgement, and social interaction. It also leads to fewer new brain cells being made in the hippocampus. This means chronic stress might make it harder for you to learn and remember things, and also set the stage for more serious mental problems, like depression and eventually Alzheimer’s disease.

It’s not all bad news, though. There are many ways to reverse what cortisol does to your stressed brain. The most powerful weapons are exercise and meditation, which involves breathing deeply and being aware and focused on your surroundings. Both of these activities decrease your stress and increase the size of the hippocampus, thereby improving your memory.

So don’t feel defeated by the pressures of daily life. Get in control of your stress before it takes control of you.

From the TED-Ed Lesson How stress affects your brain - Madhumita Murgia

Animation by Andrew Zimbelman

Researchers: Eating too much fat can injure parts of your brain

C is for Uh-Oh: Medical researchers have found that within 24 hours of a high-fat diet, there is measurable damage in the brains of rodents and humans. “Obese individuals are biologically defending their elevated body weight,” said Dr. Michael Schwartz, a professor at the University of Washington. The study indicates that eating fat leads to changes in the brain, and in the body, because it affects the hypothalamus, which regulates weight. source

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Fat signals control energy levels in the brain

An enzyme secreted by the body’s fat tissue controls energy levels in the brain, according to new research at Washington University School of Medicine in St. Louis. The findings, in mice, underscore a role for the body’s fat tissue in controlling the brain’s response to food scarcity, and suggest there is an optimal amount of body fat for maximizing health and longevity.

The study appears April 23 in the journal Cell Metabolism.

“We showed that fat tissue controls brain function in a really interesting way,” said senior author Shin-ichiro Imai, MD, PhD, professor of developmental biology and of medicine. “The results suggest that there is an optimal amount of fat tissue that maximizes the function of the control center of aging and longevity in the brain. We still don’t know what that amount is or how it might vary by individual. But at least in mice, we know that if they don’t have enough of a key enzyme produced by fat, an important part of the brain can’t maintain its energy levels.”

The findings may help explain the many studies that show a survival benefit to having a body mass index toward the low end of what is considered overweight.

“As we age, people who are slightly overweight tend to have fewer problems,” Imai said. “No one knows why people categorized as being slightly overweight tend to have a lower mortality rate. But our study suggests that if you don’t have an optimal amount of fat, you are affecting a part of the brain that is particularly important for controlling metabolism and aging.”

Imai and his colleagues study how cells produce and utilize energy and how that affects aging. Past work of theirs and others demonstrated the importance of an enzyme called NAMPT in producing a vital cellular fuel called NAD. Traditionally, NAMPT is thought to be important for making this fuel inside cells. But Imai and members of his team noticed that fat tissue churned out a lot of NAMPT that ended up outside cells, circulating in the bloodstream.

“There’s been a lot of controversy in the field about whether extracellular NAMPT has any function in the body,” Imai said. “Some researchers have said it’s just a result of leakage from dead cells. But our data indicate it is a highly active enzyme that is highly regulated.”

Such fine-tuned regulation suggests secreted NAMPT is doing something important somewhere in the body. To find out what that is, the researchers raised mice that lacked the ability to produce NAMPT only in the fat tissue.

“We were not surprised to see that energy levels in the fat tissue plummeted when fat tissue lacked this key enzyme,” Imai said. “Other tissues such as the liver and muscles were unaffected. But there was one distant location that was affected, and that was the hypothalamus.”

The hypothalamus is a part of the brain known to have important roles in maintaining the body’s physiology, including regulating body temperature, sleep cycles, heart rate, blood pressure, thirst and appetite. Mice with low NAMPT in fat tissue had low fuel levels in the hypothalamus. These mice also showed lower measures of physical activity than mice without this defect.

Their findings suggest that fat tissue communicates specifically with the hypothalamus, influencing the way the brain controls the body’s physiologic set points. Indeed, past work from Imai’s group also supported an important role for the hypothalamus in whole body metabolism. They showed that increasing the expression of a protein called SIRT1 in the mouse hypothalamus increased the mouse lifespan, mimicking the effects of a calorie-restricted diet.  

Imai suspects that all these processes influence one another. Their past work on the hypothalamus also had shown that SIRT1 function is dependent on energy levels in cells. And the new paper links energy levels in the hypothalamus to the fat tissue’s newly identified function.

After examining what happens to mice with fat tissue that doesn’t make NAMPT, they performed the opposite experiment, studying mice that produced more NAMPT in fat tissue than is typical.

Mice that expressed high levels of NAMPT in the fat tissue were very physically active. Their activity levels were especially pronounced after fasting. The mice with low NAMPT in the fat tissue became even more lethargic after the fasting period. The mice with an overabundance of NAMPT in the fat tissue appeared unaffected by the period of time without food, remaining at activity levels similar to normal mice without food restriction. In fact, the mice with a lot of NAMPT produced in their fat behaved very similarly to the mice with a lot of SIRT1 in the brain.

Imai said they are now studying whether an overabundance of NAMPT in the fat increases lifespan, as they showed in the mice with an overabundance of SIRT1 in the brain.

The researchers also found they could temporarily boost the physical activity of the mice with low NAMPT in the fat tissue by injecting NMN, the compound that the enzyme NAMPT produces. Imai is investigating NMN as a possible intervention in diseases associated with aging.

Imai speculated that this NAMPT signal from the fat tissue, especially in response to fasting, may serve as a survival mechanism.

“This phenomenon makes sense in the wild,” Imai said. “If you can’t get food and you just sit around and wait, you won’t survive. So the brain, working in conjunction with the fat tissue, has a way to kick in and let you move to survive, even when food is scarce.”

In the hypothalamus we take small chain proteins called "peptides" and we assemble them into certain neural peptides, or neural horomones that match the emotional states we experience on a daily basis.

The cells are yelling up to the brain saying, we haven’t gotten our fix today, and it’s going to start sending impressions to the brain, and the brain is going to start formulating imagery. It’s going to sound like voices in our head, to think of a reason why we should be depressed, think of a reason why we should be confused, think of a reason for our own suffering. And the body is going to be telling the brain that it’s not getting its chemical needs met. And so the brain will then activate and start going to our past situations and flashing pictures to our frontal lobe. But my definition of an addiction is something really simple; something that you can’t stop. We bring to ourselves situations that will fulfill the biochemical craving of our body, by creating situations that create our chemical need. So my definition really means that if you can’t control your emotional state, you must be addicted to it.

This is a vector illustration showing the physiological relationship between the thyroid gland, the pituitary gland, the hypothalamus, and the body’s peripheral tissues. I did it for an endocrinology journal around 1995, with a pretty early version of Adobe Illustrator, probably 5.0? (That’s 5.0, not CS5!) This illustration had to be done with a vector application because I used the pieces to animate it later. Today this kind of animation might be done with Flash, but back then I used an application called Director. I remember having to learn Director on the spot when a client before this one asked if I could animate one of my illustrations. I said “Yes!” knowing full well I’d have to learn Director that night. Talk about living by the seat of my pants. Well, it worked. I learned it very quickly (and frantically). I’d like to post my old animations some time, if I can figure out how to get them off the Syquest disks.