Cobbers on the Brain – Page 52 – Student Commentary on the Neurological Sciences

Late Night Television and Obesity

Posted on December 1, 2019 by / 0 Comment

If you have ever had trouble sleeping, you most likely watched late-night television in order to fall asleep. The commercials televised in the wee hours of the morning often display miracle products, several being diets and weight loss supplements. These products often fail as obesity is a complex disorder caused by several factors. Recent studies have shown a correlation between the inflammation of the hypothalamus and obesity. The cause of this inflammation is still being examined, but one leading cause seems to be the impairment of leptin and insulin signaling.

Understanding the function of the hypothalamus in obesity is crucial for the development of a cure. Early lesion experiments revealed that alteration in the hypothalamic region of the brain resulted in changes in feeding behavior and energy expenditure. Two types of neurons are responsible for this regulation. AgRP neurons control food intake while POMC neurons decrease food intake and increase energy expenditure. Leptin and insulin play major roles in the homeostasis of both neurons. An improper balance of leptin and insulin or ineffective leptin and insulin signaling corresponds to an increase in food consumption and simultaneous decrease in energy expenditure. Studies have shown diets rich in saturated fatty acids cause activation of cytokines and inflammatory pathways, which disrupt leptin and insulin signaling in the hypothalamus. The activation inflammatory pathways lead to transcription of genes like SOCS3, leading to more cytokines and inflammatory signaling. This leads to the chemical hardwiring of the brain to eat more food, making losing weight a massive challenge. The figure below demonstrates some of the neurochemistry of obesity.

This research does however lead to several possible treatments of obesity. Administering medication that prevents the transcription of inflammatory genes and hinders cytokine and inflammatory pathway signaling are two viable treatment options. Several studies have shown using anti-inflammatory medication such as Tylenol can decrease weight gain. The simple solution would be to prevent over nutrition or limit saturated fatty acids. However, this may not be as simple as it appears. Currently cheapest and affordable foods, those purchased most frequently by the public, are high in sugars, carbohydrates, and fatty acids. Only individuals with money can afford to purchase fresh fruits and vegetables. This leads to a social and economic dilemma regarding weight gain and obesity. Furthermore, the human body was designed from an evolutionary standpoint. In other words, the ease at which food can be obtained and consumed today, compared to the hunter-gatherer lifestyle, raises the risk for obesity.

The issue of obesity is complex. Studies have shown a correlation between hypothalamus inflammation and the disease. It is hypothesized that inflammation occurs because of an imbalance or impaired signaling of leptin and insulin, leading to inflammatory responses. Treatments of obesity vary in their approach; however, mediation of inflammatory genes and pathways has shown promising results. Factors outside the physiologic domain must also be examined. Several economic and societal facto directly impact obesity. Understanding the complexity of the disease is imperative for one day finding a cure.

Sources

https://moodle.cord.edu/pluginfile.php/798963/mod_resource/content/2/inflammation%20and%20MD%202017.pdf

Community/Disease/Health

A Public Health Crisis: The Shocking Relationship Between Type Two Diabetes and Alzheimer’s Disease

Posted on December 1, 2019 by / 0 Comment

Dementia and diabetes are two of the most prevalent health problems facing the world today. Countless resources are spent on treating the symptoms of each, though no clear cause is known for either.

Type two diabetes occurs when blood glucose levels are too high. Blood glucose is the primary way your body gets nutrients from the food you eat. Symptoms of diabetes include:

excessive thirst and urination
blurred vision
increased hunger
unexplained weight loss
tingling or numbness in hands or feet
sores that do not heal

The latter two more commonly occur in prolonged untreated diabetes which often results in greater severity of symptoms.

Risk factors for diabetes include:

age 45 or older
have a family history of diabetes
overweight or obese

One of the most interesting aspects of this relationship is the idea of leptin signaling. Leptin is a hormone released to regulate energy expenditure. In simple terms, leptin tells you to stop eating. Leptin levels are correlated closely with body weight. When diabetes leptin signaling is impaired, people can develop leptin resistance which is often correlated with insulin resistance. Insulin is a growth hormone involved with turning nutrients into useful energy for the body. When the body no longer reacts to insulin, it is called insulin resistance. In the brain, when this happens the impacts can reach the hypothalamus. This body-brain connection has been theorized to be an important link in understanding the relationship between increased risk of Alzheimer’s disease in individuals with type 2 diabetes. First, let’s talk a little bit about what Alzheimer’s disease really is.

Alzheimer’s is a neurodegenerative disease that results in memory loss. It occurs primarily in the older population but a few cases of early onset Alzheimer’s have been reported. There are two main theories behind the cause of Alzheimer’s. Neurofibrillary tangles are one whereas ABO plaques are another. In simple terms, the brain begins to lose some of its primary structure and tissue begins to accumulate before being “cleaned up” by microglia in the brain. This “cleaning up” often results in a loss of a large portion of brain tissue. Symptoms of Alzheimer’s disease include:

Memory loss
Difficulty solving problems
Aggression
Confusion
Difficulty planning events
Personality changes

There is a strong positive correlation between Alzheimer’s and Type two diabetes, though the exact signaling mechanism is still unknown. Release of insulin has been shown to improve longevity and flexibility of neurons through insulin receptors in the brain. Studies also revealed that many individuals with Alzheimer’s had impaired insulin pathways, though the exact correlation between the two diseases is yet to be fully understood. An article aimed to look at this relationship in a comprehensive way, not only studying the relationship, but looking for ways to better treat these diseases and expand the knowledge to the relationship between metabolism and neurobiology. The final message was clear: Each of these diseases needs more research. There is clearly a relationship between the disorders, but understanding just how to use this relationship requires greater research into such devastating health conditions in the world today.

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Addiction: A choice, a disease, or a different problem altogether

Posted on December 1, 2019 by / 0 Comment

Addiction today is such a common issue, and everyone seems to have a different take. People talk about whether it’s a disease or choice holding to their convictions as if letting go would send them to drown deep in the see. We see “addicts” as untrustworthy, lacking impulse control, and self-destructive, but when we look at the science it is undeniable that this thing we call addiction is so much more than just a consequence of choice or a disease with a straightforward treatment. Addiction is complex, so treatment must be as well.

Dopamine: Methamphetamine, Heroin, and Cocaine

Let’s begin with what drugs do in the brain that makes them “addictive.” Specifically, methamphetamine, heroin, and cocaine all have similar consequences in the brain. Each drug acts by causing the brain to release excess dopamine. Dopamine is a neurotransmitter often thought of as a “happy” chemical in the brain. In reality, it’s a little more complex. Dopamine is largely responsible for motivation and reward which leads to the high that a drug provides. Drugs like cocaine, heroin, and methamphetamine active the brain’s reward pathway in the VTA and nucleus accumbens. This means that the activity of using is reinforcing to the brain. After activating this pathway, people want to do it again and again because it is motivating and rewarding. Any addict will tell you that drugs became the most important thing in their lives. They chose is over everything else.

So, why are some drugs more addictive than others?

This is where complex neuroscience can be broken down into a few simple principles. Cocaine, heroin, and methamphetamine all cause an increase of dopamine in the brain. The method of action, though, is quite different. Cocaine and heroin act on just one step in the path for dopamine to be released and absorbed in the brain. Methamphetamine, on the other hand acts on all these steps in addition to a few more. More dopamine leads to a stronger high and more motivation and reward feelings. Now, we can all agree that lots of happy feeling would be appealing, but we aren’t all addicted to these drugs. Even more important, not all who use these drugs become addicted to them. According to the CDC, approximately 0.6% of the population used methamphetamine while 0.4% had some kind of use disorder. Despite being one of the most addictive substance known about in modern day, not everyone became addicted.

Why do some people get addicted and others don’t?

This is where the answer gets rather complex. Addiction is caused by physical changes in the brain as a result of long-term use. Dopamine is what is referred to as an excitatory neurotransmitter. This means that release of dopamine in the brain causes a series of actions to occur rather than inhibiting action that is already occurring. When excess dopamine is released, parts of the brain are overstimulated. This overstimulation leads to structural changes in the brain. These structural changes are what “defines” addiction from a neuroscientific perspective.

What do we do?

There really is no perfect solution to a problem as complex as addiction. However, there are a few vital pillars in combatting the problem. The first is education. Programs in schools today attempt to scare people about the use of drugs. They don’t educated people on what drugs actually do and the scare tactic, quite frankly, doesn’t work. Instead, education needs to revolve around the problems discussed above. Predisposition and understanding of your personal risk are vital to preventing addiction. Another less common approach is decriminalization. Portugal first decriminalized drugs in 2001 after the devastation of the opioid epidemic. Prior to 2001, Portugal had similar policies to America; drug education was minimal and highly criminalized. When the law went into effect, 1% of the population was addicted to heroin. Drug deaths have decreased by more than 4 times and new instances of HIV/AIDS as a result of drug use has dropped 95%. It is important to acknowledge that decriminalization is not legalization. Instead, personal use of a drug requires an assessment to determine whether treatment or a fine is the best course of action. Selling of a drug and possession of large amounts with intent to distribute is still illegal in Portugal. Such a complex problem warrants a rather complex solution, likely requiring a substantial shift in social perception and desire to help rather than judge.

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Obesity – More Than Just Food and Activity Levels

Posted on November 29, 2019 by / 0 Comment

Most people know that the initiative of former First Lady Michelle Obama was Let’s Move. One of her goals was to help a new generation of kids grow up knowing the benefits of exercise and a healthy diet and how to apply it to their lives. Instilling such habits when young and being consistent into adulthood can be very beneficial and a vital part of people’s fitness (being fit is not the same as being “skinny” though). However, many people don’t start exercising and eating healthy foods until later in life, specifically as a means to lose weight. This can be an oversimplified understanding of the way obesity works because while these adjustments can definitely help with weight loss, they do not necessarily work for everyone. (Nor should people be expected to lose weight simply because they do not fall into the “Normal” BMI range, but issues with this categorization are a separate topic.) Regardless, a possible explanation for difficulties with losing weight can be found in the brain.

The Science

Within the brain region of the hypothalamus exists a neuronal circuit called the melanocortin system with two subsets of neurons: AgRP and POMC. At homeostatic functioning, insulin and leptin inhibit AgRP neurons within this system to decrease energy intake and instead activate POMC neurons to increase energy expenditure. However, an HFD (high fat diet) can significantly reduce hypothalamic sensitivity to insulin (even after only three days) and may contribute to the development of insulin and leptin resistance. This resistance may be restored by unsaturated fatty acids like omega-3.

However, saturated fatty acids can trigger inflammatory signaling which, when prolonged, can lead to cell death in the hypothalamus, specifically in POMC neurons. HFDs and overnutrition can also cause oxidative stress in neuronal cells and consequently metabolic syndrome. An interesting fact is that hypothalamic inflammation, and thus possibly metabolic dysregulation, occurs before significant weight gain, meaning that once weight gain does occur, it might already be very difficult to lose it again and restore the original homeostasis in the brain.

Other Issues

This science explains why it may be more difficult for some people to lose weight. But if overnutrition or high fat diets can induce metabolic dysregulation and issues surrounding obesity, why do we consume “unhealthy” foods anyway?

Well, there are a number of possible reasons… Sometimes we indulge in unhealthy food simply because it tastes good and we crave it. Sometimes we are in a rush and only have twenty minutes to eat, so we buy fast food. But oftentimes, there is more to it than that, especially in different segments of the population.

Food availability and financial insecurity are two factors that can influence what types of food a person ends up consuming. Many people in the United States live in poverty or financial insecurity, and when unhealthy processed food is cheaper than healthy fresh food, people are more likely to purchase the box of mac-‘n-cheese or canned beef stew instead of fruits and vegetables or chicken breast. A further issue we encounter in connection to this, is that impoverished areas are often considered to be “food deserts”, meaning that there is less access to fresh foods because it is less available compared to urban or suburban settings. Therefore, even if people wanted to make healthy choices in terms of their diets, it may simply not be possible or feasible for them. This is where policies, incentives, or government-run programs may be beneficial. Let’s Move was a first step (the program also attempted to improve accessibility and affordability of healthy foods), but there is more to be done.

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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.

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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.

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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.

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“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/

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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.