What Comes First? Bacon or the Brain

Posted on November 28, 2019 by / 0 Comment

Bacon wrapped steak, bacon wrapped burger, bacon wrapped pork chop so why not a bacon wrapped brain? Literally anything can be wrapped in bacon. Even though bacon is delicious, along with all of the other fatty foods we eat, we definitely shouldn’t eat it with every meal. High fat diets have been linked to brain damage, type 2 diabetes, insulin resistance and more. This is why doctors across the country and even the world, are telling us to stop eating fatty foods frequently. Yes, there are good fats and bad fats, but constantly consuming good or bad harms your body. In fact, it may actually be your brain that is taking the brunt of the high fat diet.

The brain is complex. There are many different neurons and a variety of signaling pathways a stimulus can take to make your body do what it does. Even deeper in the brain, you have chemical signals and responses. Let’s dive deeper into what happens when you eat a high fat diet and why you constantly want to eat.

Imagine taking a bite of a nice juicy bacon burger. When you ingest this high fat food, your body reacts by inducing an inflammatory response pathway in the hypothalamus. This binds to a toll-like receptor (TLR) which is a protein that plays a key role in the immune system. When we think of the immune system, we typically think of a cold and how the body reacts by producing more mucous, a sore throat, and how it pretty much attacks itself. This sort of happens in the brain, but on a much smaller level. In the brain, IKK is produced. IKK is a response to inflammation which triggers NF-kB. This then makes its way to the nucleus to induce transcription. Here, it triggers more cytokines called TNF-alpha which bind to more receptors. This creates a negative feedback loop that is hard to stop because all you want to do is eat because the receptor is constantly saying “KEEP EATING!”. IKKβ is the big red light blaring this, which increases food intake, body weight gain, and also interrupts insulin and leptin signaling. So, different than making mucous, it makes you want to eat more and inflames your neurons. Inflammation in a neuron is actually the wearing down of myelin and the wearing down inside the neuron itself. This wearing down effects the endoplasmic reticulum, and causes oxidative stress. It may seem like this is never ending, but there are solutions.

A good way to help prevent this problem and still enjoy the occasional slice of bacon or high fat food is to exercise. Exercise has been proven to increase anti-inflammatory cytokines interleukin 10 and interleukin 6. These cause a decrease in hypothalamic inflammation and reduce the risk of being diagnosed with type 2 diabetes, insulin resistance and more health problems. Another way is to eat healthier. Toss in a variety to your meals, fruits, vegetables, oats and more. A steady, slow intake of high fats is much healthier than a fast, high intake. After all, slow and steady wins the race. Or in this case, slow and steady means you get to keep eating these foods later in life.

Uncategorized

Eating to Live or Living to Eat?

Posted on November 26, 2019 by / 0 Comment

Artstract by Allegra Bentrim

Leptin and Insulin in Metabolic Homeostasis

Recent neuroscience has uncovered mechanisms of how unhealthy eating habits affect our brains. Eating a diet high in saturated and trans fats leads to long term potentiation of reward pathways that eventually cause morphological adaptations of the neurons involved. The melanocortin circuit is heavily influenced by what we put in our bodies. This pathway including the hypothalamus in the brain involves two important metabolic hormones called insulin and leptin. Insulin is a hormone synthesized in and secreted from the pancreas. It is commonly associated with metabolism, healthy energy use, and healthy energy storage. Its primary job is to facilitate the entry of glucose into cells to be broken down for energy use or stored as glycogen when blood sugar levels are elevated after we eat. When it does not do its job correctly, the body is unable to maintain blood glucose homeostasis (this is what goes wrong in diabetes). Leptin is largely produced in and released from fat cells in the body, and tells the hypothalamus in the brain that the body is no longer hungry. This hormone helps the hypothalamus to regulate hunger and satiety by monitoring the amount of available energy and adipose stores. When you have just eaten, the fat cells in your body will release leptin to tell your brain that it is not hungry anymore, and the hunger response will be inhibited. Both insulin and leptin are circulated at levels that match the body’s current nutritional state. They are both released when the body is at high levels of energy availability. Both insulin and leptin are affected by the foods we eat, and a diet consisting of a lot of high fat foods will eventually cause insulin and leptin resistance. The biggest consequence of insulin resistance is the development of type II diabetes, and occurs when the amount of energy consumed overcomes the effectiveness of the hormone (see my earlier post about Type II Diabetes for more information!). Leptin resistance, on the other hand, causes the melanocortin circuitry to shift such that your brain can keep telling you that you are hungry even after you have consumed enough energy. Individuals who experience leptin resistance lose the ability to discriminate between feelings of hunger and feelings of satiety.

High Fat Food as an Addiction

The hormone leptin does a good job of maintaining the state that your body is at: when it works, it prevents hunger signals from being sent when you are not hungry. However, the amount of leptin released is proportional to the amount of body fat on an individual because it is made in and released from adipose tissues. This makes weight loss hard because a loss of weight decreases the satiety signal that leptin produces which in turn means that an obese individual trying to lose weight would experience stronger feelings of hunger. Just like with conventional addictions, withdrawals from increased hunger signals and high fat foods is difficult to overcome. Obesity and food disorders are made more difficult to manage because every body needs food to live and our society markets the high fat foods cheaper and more accessible than healthier foods.

How full are you?

Your body will start sending signals to stop eating when it is full, regardless of the caloric intake of the food you have eaten. When you eat 400 calories of dense, high fat foods like burgers and fries, they take up less space in your stomach, and as a result you feel less full from that amount of food compared with the same caloric value of vegetables and leafy greens. 400 calories of kale looks a lot different than 400 calories of pizza! The kale is less dense and will be more spread out in your stomach. Because a lower number calories of veggies fill you up than high fat foods, a meal with high fat content will leave you feeling a lot less satisfied. If you eat until you are satisfied, then you will have consumed many more calories to feel full.

Uncategorized

A Christmas Carol and Inflammatory Signaling

Posted on November 26, 2019 by / 0 Comment

It’s finally November, nearly Thanksgiving, time for stuffing, turkey, and other delicious, unhealthy foods. Then after it all, we can pack it up and break out the Christmas decorations.

One of the most famous Christmas stories is Charles Dickens’ A Christmas Carol. Every year thousands of community theaters do a production of the play and people watch one of the countless movie adaptations. At this point, most people are familiar with the famous line the Ebenezer Scrooge says when two men come asking for donations to the poor “Let them die and decrease the surplus population.” Throughout the story, Scrooge learns the error of his ways and in classic Dickens fashion comes to understand that people are in poverty not because of personal choices, but rather because of issues beyond their control.

The same is the case for obesity. Recent discoveries indicate that this issue may not be as simple as choosing to eat healthier. Obesity, and related metabolic disorders, are really the work of complex mechanisms within the brain.

The Science

The hypothalamus is a tiny region in the brain that performs a variety of functions, including controlling hunger and metabolism. Within the hypothalamus are two kinds of neurons: POMC and AgRP neurons. Under normal conditions, the POMC neurons are activated, releasing alpha MSH from the downstream MC4R neurons. This stops us from eating so that we can have a good balance between energy expenditure and food intake.

However, in cases of insulin and/or leptin resistance the AgRP neurons are never inhibited and the POMC neurons are not activated. The signal to stop eating is never sent.

How Insulin Works

Insulin normally binds to a special kind of receptor called the RTK receptor. These receptors then autophosphorylate and dimerize (come together). This process activates IRS ½ which can then activate p85 and PI3K. PI3K can then make PIP2 which can be made into PIP3. Increased concentration of PIP3 attracts a few other important proteins to the region, mainly PDK1 and AKT. PDKI1inhibits AKT, which then inhibits AS160. It is this inhibition that allows the transporter of glucose (Glut4) to enter the membrane and draw glucose from the bloodstream.

What Goes Wrong

A high fat diet has been shown to trigger the inflammatory response. This inflammation is less of the rash and cut kind. Instead it puts the brain in a state of chronic stress that impairs cognition and only exacerbates the problem of overeating.

The Toll-like receptor 4 (TLR4) is activated by saturated fatty acids. This receptor is then able to activate MyD88 and eventually IKK beta. IKK beta is then able to remove I kapa beta from DNA and activate the transcription factor NF kapa B. This transcription factor helps transcribe genes associated with inflammatory cytokines, small proteins that are able to inhibit insulin signaling in the neuron.

TNF alpha is another inflammation pathway. This pathway activates the JNK protein which is then able to block the IRS signaling cascade by inhibiting PI3K. Insulin does not have desired effect and the signal to stop eating is not sent.

Other Mechanisms

Below is a schematic from Hypothalamic Inflammation in Obesity that summarizes the effects of overeating. In addition to the pathways described above, a high fat diet changes what neurons are made and how much energy is spent. Too many fatty acids leads to not enough energy spent, forcing the body to take in more food. This leads to and is exacerbated by insulin and leptin resistance.

[1]

[1] Hypothalamic Inflammation in obesity and metabolic disease Alexander Jais and Jens C. Buning

What does this all mean?

Obesity is a complex problem with various neural mechanisms. Each of these pathways serves to worsen the problem of overeating. Based on the science, overeating is a very hard cycle to breakout of. It is not simply the result of personal choices, but rather the brain slowly destroying itself.

If this is true, then we must make like Ebenezer Scrooge does at the end of A Christmas Carol and recognize that this situation is much more than simple personal choices. It is something bigger than ourselves.

This research is still fairly new and there is still a lot to be learned. But, this research could give hope to some people. A pharmaceutical could be developed that acts on these mechanisms, making overeating an easier cycle to escape. However, this can only be done if we come to accept that both the gravity and hope of the situation.

Uncategorized

“Things I Wish People Knew* Concussions”

Posted on November 25, 2019 by / 0 Comment

*About (See that’s the concussion doing it’s thing)

For this blog, I will again include potential symptoms as well as neuroscientific aspects behind concussions. However, I first want to focus on some other information provided to me by a friend currently dealing with a concussion. Hopefully this will prove to be equally, if not more, beneficial to you. Wishing her a steady recovery, here are 10 things my friend wishes people knew about concussions:

Every concussion is different. One experience (maybe your own or one that you’ve heard about) is not necessarily generalizable to others’ experiences. It’s really hard to understand what it’s like until you’ve had one.
It may be a moot point, but you can’t see concussions. Therefore, even if someone seems fine, it doesn’t necessarily mean that they are.
Concussions make everything harder, especially because they never really “turn off” and your head constantly either hurts, has pressure, or feels foggy. While it varies from person to person, concussions can make reading, seeing, writing, listening, thinking, sleeping and, therefore, just existing hard. It makes you feel helpless.
Have compassion, be patient, give endless amounts of love. Having a concussion can make people feel isolated and alone because they have to spend a lot of time in quiet environments, which can often mean by themselves. For people in your life who struggle with mental health, all of that forced alone time can especially take a toll.
Be there for your loved ones with concussions, but try to avoid frequently asking “How’s your head?” or “How are you feeling?”. Of course, it’s important to show that you care and to let them know that they can talk to you about their struggles any time. But on the other hand, they are constantly dealing with their concussion and probably would appreciate a different topic of conversation once in a while!
Instead of making people feel guilty, be conscious of people’s concussions because they have no control over the symptoms. Trust that they are fighting and handling life as best they can, even though you may not see it. They are probably already pushing their brain to do more than it should. It’s not their fault that they are not able/ supposed to do certain things (like use technology, watch movies, or be in a loud environment).
Concussions are not about “just working hard” and “pushing through”. Pushing through is painful, not productive and not helpful in the recovery process.
Symptoms can rapidly and unexpectedly change. Someone may be feeling alright one minute, but not so much the next. This can be applied to the recovery process as well because it is often not linear.
Never make the person with the concussion feel like they need to “prove” their injury to you. Believe them. Especially when it has already been diagnosed.
Support them. Love them. Hugs galore (if they like hugs).

After providing this advice based on personal experience, the information below covers some of the medical and scientific aspects of concussions.

Types, Causes & Symptoms

Causes of concussions are usually significant blows to the head or upper body, sudden acceleration or deceleration of the head, or blast injuries. These also mark the different types of concussions the brain can experience, depending on the nature of the event. Getting any one type of concussion can occur in a wide variety of circumstances.

Image Source

Risks

One of the circumstances in which concussions are most well known to occur is football. Lots of research has been conducted for this sport specifically (especially surrounding CTE), but contact sports in general (such as hockey, rugby, soccer, boxing, etc.) pose increased risks for getting a concussion. Furthermore, they are commonly diagnosed in the military as well from events as simple as falling to something as serious as bomb blasts.

Of course the general population can suffer from concussions due to falling as well, but also due to many other incidents like motor vehicle collisions, pedestrian or bicycle accidents, or physical abuse. Having had a concussion before also makes it easier to sustain a second concussion, while possibly making the symptoms more severe as well.

Symptoms

The symptoms and potential consequences of concussions are numerous and may include seizures, loss of consciousness, memory loss, nausea/ vomiting, headaches, mood changes (irritability, anxiety, depression), sensitive vision and hearing, difficulties with physical coordination, memory and concentration issues, lethargic or easily fatigued, trouble sleeping and waking up.

Science of Concussions

There are many different findings within concussion research as to what the biological/ neural expression of a concussion could look like. One such finding is that mechanoporation (small pores or defects in the membrane) can lead to potassium efflux out of and sodium & calcium influx into the neuron, as well as hyperacute indiscriminate glutamate release. This increased firing of neural cells can then lead to a “depression-like” state, where the firing is less likely, which could be the reason for some of the postconcussive impairments.

After this increased firing, ionic pumps are actively trying to restore ionic homeostasis of the cell. However, these pumps require energy in the form of ATP (adenosine triphosphate), which means that cellular storage is often strained or even depleted and hyperglycolysis occurs (increased glucose utilization two standard deviations above normal) in order to restore ATP levels.

Other pathologies can include cytoskeletal damage, which means that the structural integrity of neurons is lost and in severe cases can lead to axonal disconnection, leading to difficulties in axonal transport. Neurotransmission is also altered due to changes in the composition and function of glutamatergic NMDA receptor subunits. Under some circumstances inflammation and cell death can occur as well. For more information on the science click here.

Disease/Health

The SAD American Diet

Posted on November 25, 2019 by / 0 Comment

Obesity rates are skyrocketing in America today and people can point many directions for the cause. Maybe we’ve just gotten lazy? Maybe we don’t have enough time/money to eat healthy? Maybe we aren’t exercising enough? While all these factors are contributing to this epidemic where almost 40% of Americans are obese, there is one biological factor we are missing; how our SAD diet affects our brain.

SAD is an acronym nutritionists have come up with meaning “Standard American Diet”. This diet is characterized by a high intake of processed foods, sugar, fried food, refined grains, high-fat dairy products, and red meat. The Center for Disease Control has found that 9 out of 10 Americans don’t reach the minimum standard for the daily intake of vegetables. Eating all this junk and skipping out on our veggies has led has taken a serious toll on our brains. Not only do physical changes happen in our body, but in our brain too.

After only three days of eating a high-fat diet (our Standard American Diet), scientists found that insulin resistance was reduced in the hypothalamus. Similarly, inflammatory cytokines were inflaming those same pathways. When we develop a resistance to insulin due to inflammation, this leads to an inhibition of PI3K in the insulin pathway. When this occurs, PI3K cannot activate AKT and FOXO1 can’t be removed from the nucleus. FOXO1 in the nucleus inhibits POMC gene expression and inhibits AgRP/NPY. If FOXO is not removed our, AgRP neurons can be stimulated and those are the neurons that make us feel the need to eat. Essentially, when we eat this high fatty diet, we are creating inflammation in our brain that is only encouraging us to eat more and more. It’s a difficult cycle to jump out of.

Many treat obesity as a choice but the science makes it clear there is more at work here than just not having enough will power to stop eating junk food. The food we eat is making changes in our brain, encouraging us to eat more rather than telling us we are satiated.

Studies of obese participants vs non-obese controls have found a number of changes in the brain using neuroimaging techniques. Using fMRI, scientists saw that obese women saw greater activation in their putamen, an important area in the brain for reward when presented with pictures of high-calorie foods and eating utensils compared to lean women. This suggests that obesity has also created heightened responses to visual stimuli regarding food, especially in areas of reward and motivation which is another example of our brain working against us once we are obese to keep us that way.

So, the next time you think obesity is all about choice, make sure you consider the other factors that may be contributing. It’s not as black and white as it may seem. Once you’ve gotten to the point where your brain is actively encouraging you to eat more and responding positively in your putamen to food cues, it’s a tough habit to quit that SAD diet.

https://www.cdc.gov/obesity/data/adult.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241905/

Uncategorized

Obesity Below the Surface

Posted on November 24, 2019 by / 0 Comment

See the source image

Obesity and Inflammation

Inflammation occurs in response to any kind of harmful stimulus. Think of when you get a scratch, the area around it becomes, warm, red, and inflamed. This is a good example of the inflammatory response. However, inflammation can also happen in the brain in response to potentially harmful stimuli. The brain, specifically the hypothalamus can become inflamed in response to overnutrition. This inflammation occurs within a few hours to three days after an overconsumption of glucose or lipids. Inflammation in the hypothalamus can lead to dysregulation of homeostasis. Because inflammation occurs before the onset of metabolic syndrome and related illnesses, it is believed to be a cause of those disorders. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389774/#!po=6.19835

Metabolic Syndrome

Metabolic syndrome is a cluster of See the source image symptoms that lead to an increase in the risk of developing Type 2 Diabetes, Cardiovascular Disease, and stroke. The figure is a good graphic of what components are involved with metabolic syndrome. Having even one component of metabolic syndrome can increase your risk of development of a serious condition. About 1/3 of adults in the United States have metabolic syndrome. One of these components is critical in the hypothalamic inflammation that is seen in obesity, insulin signaling. https://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/symptoms-causes/syc-20351916

Insulin Signaling

https://www.ncbi.nlm.nih.gov/pubmed/28045396

Insulin resistance is a critical part of obesity and Type 2 Diabetes. When the body becomes resistant to insulin it no longer responds to insulin. The figure above focuses on insulin’s role in the activation of FOXO1. FOXO1 is critical for the activity of POMC neurons (more on that later) and when it is activated it no longer inhibits STAT. FOXO1 can be inhibited by the presence of saturated fatty acids and TNF. The figure also shows another role for saturated fatty acids, downstream activation of cytokines and a protein known as SOCS (suppression of cytokine signaling). This brings us back to the role of overnutrition in the inflammation response. The figure above also shows the role of leptin signaling. In obesity leptin signaling is also dysregulated. Normally leptin is repsonsible for the activation of POMC and the inhibition of AgRP. The last step of this signaling pathway involves STAT which can be inhibited by the inactivation of FOXO1. Obesity also manifests itself in leptin resistance. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430504/

POMC and AgRP

AgRP neuron are regulated through leptin and insulin signaling pathways mentioned above. AgRP neurons are responsible for messages telling us to feed. When this control is lost through leptin resistance, the inhibition is lost and leads to overfeeding. The other half of this control system is the POMC neurons. These neurons are responsible for telling us not to eat. They can be activated by both insulin via FOXO1 and leptin signaling. When resistance to insulin and leptin occurs these neuron become less active. The third part of this diagram shows the importance of the balance between energy expenditure and food intake. When control of POMC and AgRP is loss food intake goes up and subsequently energy expenditure decreases. https://www.ncbi.nlm.nih.gov/pubmed/28045396

There are more pieces than what meets the eye involved in obesity. Once the original overnutrition occurs it triggers changes within the brain. This becomes a vicious cycle of overeating and physiological changes which can be difficult to break out of.

Uncategorized

Obesity: Blame the Brain

Posted on November 22, 2019 by / 0 Comment

While diet fads come and go, in the end physicians typically boil there advice down to a simple statement; burn more calories than you eat and you’ll lose weight. Unfortunately, this oversimplification of a very precariously balanced regulatory system in the human body leads to a lot of shame for people who simply can’t keep the weight off. This isn’t a problem facing a few Americans, this is a national epidemic. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 1 in 3 adults are overweight, and 1 in 3 adults are considered obese meaning that a combined 2 out of 3 adults are above their normal weight based on the 2013-2014 survey. This epidemic is far too large to be placing personal blame on every individual. This is not to say that personal choice does not play a role; each and every person must make decisions to eat as healthy as possible within their means as well as dedicating time to exercising. That being said, sometimes its not enough.

What’s the brain got to do with it?

Unlike many common conceptions, obesity is not simply because people are being lazy and eating food that is bad for them. While factors such as eating habits, exercise, and screen time all contribute to a person’s weight, so do medications, chronic illnesses, socioeconomic status, and access to healthy foods. Genetic predisposition has also recently been shown to play a major role in a person’s weight. What many people don’t know is that chemical changes in the brain are partially, if not largely, responsible for obesity and can be induced by outside factors.

ER Stress May be Limiting Diet Success

Leptin is one of the main hormones in your body responsible for maintaining balance when you eat.

Lee, J., & Ozcan, U. (2014). Unfolded protein response signaling and metabolic diseases. Journal of Biological Chemistry, 289(3), 1203-1211.

It suppresses appetite and also regulates how much energy your body spends. Working alongside leptin is insulin, which allows your body to use the energy from the food that you eat. When the body becomes resistant to leptin and insulin, energy usage and eating habits get out of whack. New research suggests that endoplasmic reticulum (ER) stress induced by biochemical changes could be responsible. Check out the figure to the right for the data on this. As is shown, when a Western Diet (i.e. high in fat) increases cholesterol and free fatty acids, changes to stress states can result in increased homocysteine and a variety of other changes. This put the ER under stress, which is particularly bad because cells need a functioning ER to maintain proper proteins.

So, what’s the link to leptin and insulin? Well, once the ER is under stress, it sets off a cascade known as the unfolded protein response. In this response shown in the figure, cellular metabolism is altered, and inflammatory actions are dramatically increased.

This inflammation, specifically NF-κB proteins, alters DNA transcription and results in the transcription of SOCS, or the suppressor of cytokine signaling. This inhibits specific JAK-STAT signaling, which is the mechanism that the leptin hormone works through. This hormone is tied intrinsically to the insulin pathway, which makes the situation worse. Furthermore, this is just one small problem going on in the cell. Inflammation and other pathways and receptors are being targeted as well, resulting in massive changes to the microenvironment in the hypothalamus, the region of the brain responsible for regulating food intake. These can be seen in the figure below, with the full paper here.

Jais, A., & Brüning, J. C. (2017). Hypothalamic inflammation in obesity and metabolic disease. The Journal of clinical investigation, 127(1), 24-32.

What’s the takeaway?

Obesity is a massively complicated issue stemming from a variety of personal, biologic, and societal issues. It is causing a huge health burden to the world and especially the US. While personal responsibility in making good food and exercise choices is important, exclusive blame can’t be laid at the backs of the patients. Fast food, whether it is in a drive thru line or a box at the grocery store is changing our diets and not for the better. Understanding the complex web of factors that contribute to this crisis is a good first step. Most importantly, changing our narrative about obesity and empowering the medical community to seek out new ideas and solutions is the only way to eradicate this epidemic.

Uncategorized

The Brain on a High Fat Diet

Posted on November 21, 2019 by / 0 Comment

Do you ever crave food to the point where you are pretty sure you are addicted? Well, turns out you might actually be addicted to food. Recent studies have connected obesity and overeating to changes that manifest in the brain, specifically linked to energy homeostasis which is the balance of energy in your body. The hypothalamus in your brain is what maintains this homeostasis by regulating feeding behavior and energy expenditure, in other words when you eat and when you exercise is controlled by the hypothalamus. You may be questioning how your brain knows what the rest of your body needs, well this is through insulin and leptin signaling. Insulin and leptin begin signal cascades that lead to the response “stop eating and expend energy.”

Leptin is a hormone produced by adipocytes, fat cells, and binds to receptors in the hypothalamus. The receptor then begins a signal cascade that activates the synthesis of the neuropeptides proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcription (CART). These neuropeptides then lead to the “stop eating and expend energy” response. The leptin signal cascade also results in the inhibition of agouti-related peptide (AgRP) and neuropeptide Y (NPY) which are neuropeptides that signal the “eat now” response. This is great, because it tells your body you’re full. You have enough energy to do life. But there’s a catch! FOXO1 inhibits the action of this signaling cascade leading to the opposite response, “eat more.” To combat this, insulin steps in.

Insulin is a hormone produced in the pancreas, that also binds to receptors in the hypothalamus. Insulin initiates a signal cascade that kicks FOXO1 out of the nucleus so it can’t disrupt the leptin signaling. The figure below shows how leptin and insulin control appetite in the hypothalamus.

If there is a lack of leptin or insulin, POMC and CART will not be synthesized to give the “stop eating and expend energy” response. The figure also shows that ghrelin, produced in the stomach will also induce appetite. AgRP and NPY will be synthesized leading to the “eat now” response. If you haven’t eaten for a while and need some energy this is good. But, if this signal occurs even when you’re not hungry, then you have a problem. This uncoupling of the “eat now” response and the amount of energy one has is key in obesity.

So, how does this signal happen when you don’t need energy? Obesity leads to this disruption of energy signaling in a number of ways. One way is that a high fat diet causes the activation of inflammation in the hypothalamus which elicits a stress response from the endoplasmic reticulum (ER). ER stress leads to leptin and insulin resistance, therefore increasing AgRP and NPY neuropeptides and the “eat now” response. The body still produces leptin and insulin, but now the hypothalamus can’t send out the correct signal. This leads to overeating because an individual will continue to eat after attaining their energy threshold. In mice, the hypothalamus returned to its normal size after three days on a low-fat diet. So, no worries, one meal won’t send you down an uncontrollable food tunnel. However, prolonged high fat diets could lead to the uncoupling of energy need and feeding behavior. Therefore, proper nutrition and portions is key to maintaining a healthy lifestyle.

Uncategorized

Keep Me in Coach, I’m Ready to Play

Posted on November 20, 2019 by / 0 Comment

In America, it seems that athletics is just as stressed, if not more than, as academics. We live in a culture where professional athletes are praised and put in the spotlight, and the pressure put on them to perform no matter the circumstances is extremely high. So, despite dangerous injuries, professional athletes would often stay in the game to prove their “toughness,” and that tended to be the expectation from coaches since the inception of athletic events. Unfortunately, high school athletes who would follow professional athletes would take cue from them and buy into the idea that they should play at all costs. For specific injuries like concussions, which we now know are extremely dangerous and serious, one important question to ask is why do many high school athletes not report the symptoms of concussion?

Just a Few Reasons

Winning at all costs

High school athletics are important and are most often extremely beneficial to kids with regards to social connections, teaching discipline, and learning vital teamwork skills. However, far too often are high school athletics not kept in perspective.

When asked in a study that was published by the Journal of Athletic Training, up to 55% of high school athletes reported that they didn’t or wouldn’t report a concussion. A strong argument could be made that one contributing factor is the athletes did not want to sacrifice playing time to protect their physical health. They are taken too seriously, specifically when it comes to athletes’ injuries.

2. “I can’t let my team or coach down”

Although a noble motivation, putting the team or opinion of the coach ahead of one’s physical health is extremely risky. Many athletes feel myriad emotions when it comes to physical injuries, and a common one is that they believe they will look “weak” if they complain of pain. According to an article by Reuters Health, males especially tend to be more sensitive to how their fellow teammates and coaches view them.This is arguably due to the expectation that men are supposed to be strong and resilient, and showing emotion is can be considered a “vulnerability” in the sports realm.

3. Honest Ignorance

At higher levels of athletics like college and professional sports, the signs and symptoms of concussions are well known and monitored at the slightest instance of a hit to the head.

However, in high school athletics, strict regulations like that of college and professional sports are not uniformly enforced. This leads to high numbers of ill-informed or uninformed high school athletes and coaching staffs. Not knowing the symptoms of a concussion is dangerous, and too many kids have stated that they did not know they had a concussion while they were concussed.

The Solutions

One solution to these problems first and foremost is education. Coaches need to understand the seriousness of concussions and the lasting effects they can have, like difficulty concentrating, personality changes, difficulty with memory, and many more. These are exacerbated if and when someone sustains a second concussion, which is easier to obtain having had an initial concussion. Another point of importance to be stressed to high school athletes, parents of athletes, and coaching staffs is: keep athletics in perspective. Sacrificing enduring brain health problems for a game is never the answer. Brain injuries are unlike injuries to other parts of the body, and injuries to the brain must be treated accordingly. Not to diminish the importance and amazing accomplishments to be had in high school athletics, but after all, it is just a game.

The Science

Many things have been studied that occur after a significant impact to the head is sustained. After impact, potassium flows out of the cell while sodium and calcium flows into the cell, and this is allowed because of defects in lipid membranes that occur after the trauma. This causes an ion flux and a subsequent depolarization that can lead to depression-like responses that are attributed to the post-concussive impairments. To combat this, ionic pumps that require ATP are overactive, which leads to hyperglycolysis. This results in an imbalanced energy supply and demand, which ultimately leads to a variety of metabolic changes that are serious to say the least. The force of an impact can also damage the cytoskeletal structures like dendritic arbors, axons, and astrocytic processes. This often leads to the loss of integrity of axons, and in extreme cases axonal disconnection occurs. Overall, it is not just one specific thing that can be pinpointed when determining the cause for a concussion but rather many things that can and do contribute to the effects of a concussion.

Uncategorized

‘Get Your Head in the Game!’ – Figuratively, Not Literally

Posted on November 20, 2019 by / 0 Comment

CONCUSSIONS are one of the most commonly encountered sports injuries where rates are estimated at two million sport related concussions per year in the United States according to the Brain Injury Research Institute. This number is potentially much larger due to the lack of knowledge and awareness about concussion and brain injuries. There has been an increase in research attempting to understand what happens in the concussed brain, but there is a long way to go to help identify treatment plans and return to play protocols. For now, we maybe shouldn’t listen to Zac Efron and his High School Musical buddies. So let’s keep our head out of the game and, instead, focus on raising awareness about concussions and other injuries to the brain.

A vast array of symptoms that can be associated with concussions and traumatic brain injuries (TBI) are a result of the diversity and broadness of factors relating to basic neurobiology and a neurometabolic cascade. These factors include ionic flux and glutamate release, energy crisis, cytoskeletal damage, axonal dysfunction and altered neurotransmission, and inflammation.

IONIC FLUX AND GLUTAMATE RELEASE

Upon a biomechanical injury, potassium efflux and sodium and calcium influx occur due to a damaged phospholipid membrane. An efficient action potential will not be able to be produced because of abnormal depolarization from the rapid influx of sodium and calcium.

ENERGY CRISIS

In an effort to maintain cellular homeostasis regarding ionic flux, ionic pumps that require ATP are shifted into overdrive. This leads to a depletion of energy reserves, thus resulting in reduced cerebral blood flow and an imbalance between energy supply and demand. Prolonged calcium influx leads to increased intracellular calcium and greater amounts of calcium to be sequestered in the mitochondria. Too much sequestration can result in mitochondrial dysfunction which causes the energy crisis.

CYTOSKELETAL DAMAGE

The cytoskeletal structure which include microtubules and microfilaments consist of delicate and complex components. When damage is implemented to a brain region, neurofilaments can easily be phosphorylated and break. Axonal influx of calcium results in the breakdown of proteins into smaller polypeptides on cytoskeletal components. This damage makes the neurons more prone to axonal disconnection and death. After a TBI, ongoing cerebral and hippocampal atrophy may be present. The progressive atrophy can show the appearance of cognitive deficits later in life. The occurrence of a TBI before full recovery from a previous TBI may more likely trigger activation of intracellular proteases and the cascade that leads to apoptotic cell death.

AXONAL DYSFUNCTION AND ALTERED NEUROTRANSMISSION

Increased axonal permeability after a TBI is a result of the vulnerability of the axon. Consequently, this can lead to overall axonal dysfunction. A damaged neuron where neurofilaments and microtubules are altered allows for the neuron to not normally function. Injury to the axon and other white matter areas occurs along with mechanoporation, stretching of individual axons, disruption of axonal transport, axonal misshaping, and axonal disconnection.

Altered neuronal transmission is present after a TBI and occurs due to an imbalance in excitatory and inhibitory neurotransmission. This imbalance is seen due to alterations in the glutamate receptors or GABA receptors which alter excitation and inhibition. Alterations in glutamate, an excitatory neurotransmitter, affect the normal functions of calcium flux and the activation of downstream signal transduction molecules. Decreased levels of GABA, an inhibitory neurotransmitter, affect fear-based learning associated in the amygdala.

INFLAMMATION

Changes in inflammatory markers following a TBI has shown an activation of microglia in the cortex. Microglia function as macrophages in the central nervous system to mediate immune responses. Upon damage to the brain, inflammatory changes are triggered by the upregulation of cytokine and inflammatory genes. Inflammation, although an evolutionary mechanism for protection, has also been shown to induce damage to brain regions that relate to long term side effects. For example, microglial response to damage in the substantia nigra has been shown to increase risk of Parkinson’s Disease after a TBI.

WHY IS THIS SO IMPORTANT?

The research presented above sheds light onto why there are so many symptoms involved with brain injury and concussion. A list of symptoms is listed below:

Migraine headache
Photophobia and phonophobia
Vulnerability to second injury
Impaired cognition
Slowed processing and slowed reaction time
Chronic atrophy
Development of persistent impairments

Concussions affect each individual differently and symptoms depend on a number of factors including strength of trauma and the brain area affected by the trauma. When an individual is experiencing these symptoms, they must be monitored closely. Both physical and mental rest can speed the recovery of concussions. Unfortunately, there is still much more research to better understand how to prevent concussions and the symptoms associated with them.

CONCUSSIONS and any injury to the brain are not to be taken lightly. The broadness of symptoms associated can have long term affects. Management of concussions will continue to evolve as more research develops. This will allow us to better understand the steps toward prevention, treatment, and return to play protocols. Protection of athletes and all those more prone to concussion is the number one priority. If you are experiencing any of the concussion symptoms talk to a health professional and play it safe by getting your head out of the game!

For more information on the research presented, follow:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479139/

For more information on the symptoms associated with concussion, follow:

https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594