Obesity is a growing epidemic in the United States along with other parts of the world. The concern of people not being able to eat because food cost too much or because it was not excisable to people has changed the way food is made. The food industry has made foods that are cheap and very easy to get to, insuring that more people would be able to eat. However, out of these good intentions these foods are extremely unhealthy and worse addicting. Food companies knew that these foods are unhealthy so to make sure people continued to buy the foods they play around with the chemistry. They change it to the point that the food becomes drug like and once you have it the buyer wants more so the next times they see the food it triggers those feels of pleasure which makes them want to buy it. However, this cycle doesn’t end there.
Studies show that overweight parents with a disposition to eating unhealthy food change their brain biological make up. The number of disorders and diseases that occur from eating food causes heart problems, liver problems and even brain problems. The really concerning thing is that if unhealthy people have a child, that child is more likely to suffer the same problems. These problems don’t just come from eating unhealthy foods that are found in the house. They also come from a genetic predisposition to eat high fat foods passed on by the parents. Because at a young age, new born babies rapid brain development can be altered even after birth. One study showed that mice born from health parents that were raised by an unhealthy mouse have a high disposition to unhealthy foods. Their findings claim that the high fat milk form the replacement mouse genetically changes the babies want for high fat foods. But knowing this occurs in some people, does the concern arise that people will just use this as an excuse to eat whatever and blame it on a lack of willpower? Obesity can be a slippery slope because once a person goes down that path it can quickly escalade out of control.
Lithium Toxicology
Lithium is a soft metal, it is the smallest metal found on column one, row two of the periodic table. Due to its small size and plus one charge lithium is useful in the biological system. To date the uses of lithium mostly revolve around bipolar disease among other mental disorders. However, this treatment has been used for quite some time; the exact mechanism to how it works is still unknown. The main target area of lithium is the apoptotic (cell death) part of the brain. Disorders like bipolar contribute to over apoptotic which is stopped by the drugs containing lithium. Is lithium good for people to be taking?
Lithium over dosing is a more common occurrence then one might think. There are two forms of OD; the acute and the chronic. Acute OD is the taking of too much lithium in one event. This can present itself in a number of symptoms like diarrhea, stomach pains, weakness, coma, hand tremors, ataxia, seizures, etc… Chronic OD is the taking of too much lithium on a daily bases. This is a more common occurrence than acute OD because this usually means the person was unknowingly prescribed too much by their doctor. This can result in serious symptoms like kidney failure, memory problems, movement problems, psychosis, etc… Not knowing the how much lithium can cause an OD the question becomes; is it ethical to continue prescribing it to people given the symptoms?
My Brain Made Me Do It…Obesity As a Brain Disease?
America has a growing problem with obesity that raises concerns about the future health of the nation. Additional, the incidence of childhood obesity is steadily increasing as well, which puts youth at an increased risk for a number of conditions later in life including high blood pressure, high cholesterol, cardiovascular disease, type 2 diabetes, bone and joint problems, sleep apnea, and psychological problems. The cause of obesity appears to be simple: overnutrition. People are consuming more calories than they are burning off, which causes them to gain weight as body fat. But is the cause really that simple? The article, “Is obesity a brain disease” argues that obesity is caused by overnutrition but the brain may be responsible for releasing signals that propagate the biological trap of obesity.
Often, overeating and obesity is seen as an issue of lack of willpower. People are told to choose to eat less and choose healthier food options. However, scientists have found that early exposure to high-fat and high-sugar diets increases the likelihood that a person will prefer that type of diet as an adult. Even pre-natal exposure via the mother’s diet during gestation may impact the feeding behavior of an individual later in life. Preferences for high fat and sugar diets have long lasting effects for individuals. For example, glucose sensing and use of insulin is impaired in individuals that are chronically exposed to overnutrition. Dysregulation of glucose metabolism plays a role in the development of type 2 diabetes. Studies using fMRI, an imaging technique to study functionality, have found there are differences between the activity in obese brains versus normal brains. Obese brains became more activated by food stimuli and more rewarding signals were sent in the brain in response to food. What causes the differences in desires for food and activity in the brain? There are two neuron types in the brain that control appetite. POMC neurons increase appetite, and these are the neurons that are overactivated in obese individuals. On the other hand, NPY/AGRP neurons have the opposite effect of decreasing appetite and are less active in obese people than average weight individuals.
Based on these facts, things are looking pretty grim because the brain is contributing to a person’s likelihood to overeat to form a biological trap. Is there any chance to break this vicious cycle? Our class investigated several ways to treat obesity as a brain disease and break the cycle. First it has been shown that eating healthy foods decreases appetite by increasing hormone signals to the brain. Another healthy lifestyle choice includes maintaining a regular sleep schedule. Regular sleep prevents decrease in metabolic rate, increases glucose levels and changes in insulin response. POMC neurons are a potential target for pharmacological intervention. By decreasing activation of POMC neurons, appetite would be suppressed in obese people. The differences in the brain can be changed to an extent by losing weight and maintaining a normal BMI. Scientists have found that there is a difference in brain activity between individuals that successful dieted and individuals that are still obese. However, not all of the differences in the brain caused by obesity can be reversed in all cases. Ultimately, our society needs to understand the consequences of eating fast food, constantly being on-the-go, and exposing kids to unhealthy food from a young age. Education will be another important tool in breaking the cycle for future generations.
Obesity: More than Poor Nutrition and Laziness
Many people are aware of the obesity epidemic in the United States. Many people also associate obesity with extreme over-eating and rare exercise. Recently, researchers have found that obesity may be about more than just an unhealthy lifestyle. Contributing authors to the article Is Obesity a Brain Disease? argue that there are many signaling pathways in the brain that control and regulate hunger and appetite. This specific article is a review article of multiple studies that try to link actual brain signal pathways to reasons for explaining weight gain that can be linked to obesity.
One main point the article makes is that over-eating/over-nutrition is not just a choice. Some may look at that statement and disagree, but pathways in the brain have been found that show the brain is very connected to and partially responsible for the choices people make in relation to eating. The article states that predisposition to high fat diets in the womb and as a child makes them more appealing to people at older ages and actually can influence the food choices they make for their life. These high fat diets have also been linked to cognitive defects in the brain. While the article talks about the relationship between obesity, unhealthy diets, predisposition to obesity, genetics, and brain pathways, it can be hard to decide which is to blame. It is also difficult to decide which comes first, the obesity being induced by over-eating or over-eating being induced by brain function which then leads to obesity. The story is quite complicated. In my opinion the 3 most interesting things learned from this paper and this week’s discussion in class are: the positive effect of health foods, the negative effect of dysregulated sleeping, and a specific neuron called POMC and its role in regulating hunger.
Eating healthy foods that contain a high amount of fiber is really great for a person in multiple ways. Not only does it provide the body with necessary nutrients, but it also makes the body feel fuller for a longer amount of time compared to sugary and unhealthy food. It works to make the body feel full by reducing gastric emptying. It also is able to help increase hormones that curb appetite, for example glucagon-like peptide 1. This specific protein is able to curb appetite by decreasing the satisfaction the brain feels by food. This is really awesome and beneficial to society because eating healthy can do so many great things for a person, to both combat obesity or to remain healthy.
While healthy eating shows the link between obesity and brain function, I think sleep regulation and its link to weight gain/obesity really helps to show that obesity might be able to be considered a brain disease. Most people know the effect on their brain when they experience and irregular or disrupted sleep pattern. The brain is groggy, prone to headaches, and sometimes is slow to respond. This is also expressed in pancreatic insulin release. When the brain is tired and fatigued from irregular sleep, the pancreas is unable to release insulin to respond to the increased blood sugar after a meal. When this happens, the glucose is more likely to be stored instead of metabolized for energy. The body works on a 24-hour circadian clock, which is usually common knowledge, but a recent study from Vanderbilt University discovered that insulin too is able to function on a 24-hour cycle. Dysfunction in sleep and insulin release can be negative for people because it leads to unnecessary storage of glucose, slower metabolic rate, and a decreased rate of calorie burning during resting periods.
The third, and most direct, connection to obesity being a brain disease has to do with special neurons called POMC neurons. These neurons release a chemical called proopiomelanocortin which helps to decrease appetite. It uses the adrenal gland of the sympathetic nervous system to secrete its hormone. One other important hormone involved in appetite regulation is leptin. Leptin is able to alter the activity of these neurons because it is a chemical that signals fullness to the brain. Leptin activity has been seen to be lowered in obese people. This causes a negative cycle. If leptin isn’t working correctly, it can’t correctly signal to the POMC neurons to help inform the brain that the body is full and that it needs no more food.
It is a very unfortunate situation that obesity seems to be such a vicious cycle linked with both the brain and the fact that Americans, for the most part, have a reasonably unhealthy diet. The important thing to do with this information is to brainstorm solutions to the problem. One major problem the US is faced with is the price of health foods. Fresh fruits and vegetables are much more expensive than frozen or canned one. But they contain much more nutritional value. For struggling families, canned or frozen foods may be the only thing they can afford. Eating unhealthy leads to the habit of eating unhealthy, this has major effects in the brain and hormones of a person.
While it may seem like a good idea to target one of the molecules involved in hunger signaling, people in the US (and likely around the world) eat even when they aren’t hungry. Hunger doesn’t seem to be the actual problem. The public needs to be educated on the possible long term effects of obesity, healthy food choices, and the negative things happening to their body when they make unhealthy choices regarding food and eating.
Lithium: Too Much of a Good Thing
Many people have heard of using lithium as a treatment for bipolar disorder, but many people don’t know how it works in the brain to help cope with the manic phases of bipolar disorder (BD). Those confused people are in luck because scientists aren’t even 100% sure about why lithium works to treat BD. Recently scientists have taken a look at other uses for lithium in nervous system related disorders. One recent example of this can be seen in the article Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders. This study takes a look at how lithium functions in the brain and what types of pathways it affects. It also takes a look at lithium’s effect on multiple CNS diseases and concludes that lithium can be neuroprotective and antiapoptitic. Both of these outcomes result in better overall brain and CNS function for the disorder individual.
The two main ways that lithium works in the brain seem to be 1) by inhibition of the molecule GSK-3 and 2) preventing apoptosis. GSK-3 is a molecule in the brain/CNS that plays a role in many pathways. It is inactive when phosphorylated and usually leads to activation of multiple transcription factors when inactivated. One specific way this works can be seen in multiple sclerosis (MS). MS is a condition where neurons become un myelinated, which leads to loss of motor control. When lithium is used as a treatment, it is able to inhibit GSK-3, which in turn activated transcription factors that are able to aid in remyelination of damaged nerves. This is an important because remyelination can help lead to regain of motor control for MS patients. The other main way lithium works in the brain is through preventing apoptosis, or cell death.
If lithium seems to do so many good things, why isn’t it used for the go to treatment for more conditions instead if as a second, or even last, resort? In looking at the pathways that lithium effects, I think it would be safety say lithium might be dangerous since it has so many possible effects.
(a few notes about the picture… Lines ending with arrows indicate connections that activate molecules. Lines ending with a flat line mean that the starting molecule inhibits the molecule where the line ends. Dashed lines mean that lithium treatment inhibits/decreases that pathway when used as a treatment.)
Take for example the previously discussed example of GSK-3 inhibition activating a transcription factor to aid in MS, how can we be so sure that only that specific transcription factor will be activated? The picture of the many pathways clearly shows multiple effects of GSK-3 inhibition. It has even more effects that aren’t actually listed in the diagram. Now think about lithium’s inhibition of apoptosis and all the ways pictures to get to that goal. What might happen if the wrong transcription factors for disease treatment become active due to GSK-3 inhibition? What might happen if too many cells stay alive due to the lack of apoptosis and form tumors? Both if these questions seem to lack answers, at least in the discussed paper. Thinking about the widespread pathways that lithium effects lead to the discussion of these two questions which made me question if lithium is really the best treatment on the market. It seems that the multiple pathway modification aspect of this drug is unsafe. I think it might be a better idea to treat diseases by targeting a molecule further down in its specific pathway in order to allow for more precision and less possibilities for error.
One really interesting thing I learned from the lithium week discussion in my class was that the mechanism of lithium’s action in bipolar is pretty unknown. As a future pharmacist, it’s interesting to see that doctors prescribe this drug without understanding why it works. I also think it’s pretty strange that other mechanisms of lithium’s action are very well studied, but the reason it works for bipolar disorder (one of its very first uses) is still quite unknown.
A Hard Hitting Discussion: How do we effectively treat concussions?
I doubt it is surprising to find that a blow to the head can lead to some pretty serious implications in day-to-day and long term functions. Concussions seem to be the most common form of head injury and can be the consequence from a variety of activities that we choose to do. Concussions can also be referred to as mild traumatic brain injury (MTBI), which makes it sound a bit more serious. But what actually happens when you get a concussion? One tends to think of someone being knocked out or perhaps just dizzy. However, the complications brought about by concussions are much more serious. They affect an individuals ability to pay attention, to learn, and impair basic daily cognitive functions. But thankfully, the human brain is a remarkable structure and can repair itself even after a 200 pound lineman shoves his knee into your head and knocks you into tomorrow.
The real issue lies in how an individual goes about treating a concussion. Ideally, they should refrain from physical activity that would put them in any sort of intense physical contact with anyone else. It is critically important to the success of an individuals recovery that they do not obtain another blow to the head that could possibly further the damage done by the initial concussion. In extremely rare cases, an individual that takes on a second blow relatively soon after an initial concussion may actually be killed. This is referred to as Second Impact Syndrome and is largely a result of too much swelling in the brain due to traumatic events.
Given this very rudimentary information about concussions, it is important that we address concussions in an appropriate manner. In particular, sports-related concussions seem to be on the forefront of discussion. Let’s be real, if you get a concussion your first football game of your senior year season, are you going to be okay with having to sit out for several games? And what if you get another one after that? You’re most likely done for the season, and that’s a heartbreaker. But it is extremely important that you’re not exposed to further physical harm until you’re recovered, even if that’s the last thing you want to hear.
That being said, what is the real issue here? When it comes down to it, it’s easy for an individual to just brush off a concussion and act like it never happened, and this happens more frequently than we’d like to admit. Additionally, it’s often times difficult to assess whether or not an individual even has a concussion. They happen so quickly and if you retain consciousness it can be difficult to properly address what happened before the pile of guys gets up and the next play is run. Football is certainly not the only sport that this issue is a concern. What if an individual doesn’t report it? To say that a dedicated athlete is good with sitting out a few games would just be nonsense. They want to play. But how can that be healthy? Are we going to see some long term cognitive damage due to excessive and consistent concussions? Retired NFL players are coming forward and recognizing the damage done from repetitive physical damage to their heads without time to properly recover. Now that we’re having kids start playing contact sports at earlier and earlier ages, is this something we have to worry about? How will this affect their development in, for example, their learning? Are they going to start showing symptoms similar to retired NFL players in their 30’s? Or are they going to be just fine? Are we overreacting about concussions?
There have been some proposals to help curb the effects of concussions. For example, it has been suggested that indicators of how much force an individual takes upon getting hit during game play. At a certain amount of force, that individual is done for the game. Would that help or would it just take away from the actual sport? It’s not a matter of preventing concussions. They’re bound to happen. It’s a matter of how we go about treating them once they occur and seeing to it that an individual has a healthy and unhindered recovery, which is often easier said than done.
Wait, what?
One thing to know before you dive into anything on this blog. This stuff is very complicated. This weeks article in particular was very scientifically based and dense to get through. Not even science students who have been in college classes for nearly 4 years, nor their professors, completely understand everything that’s going on. The brain is an extremely complicated organ. Our goal here is to give the science in more simplistic terms, and more than that, explain what this means for us living in our society. Why should we care about this stuff?
Many of the complicated terms discussed in Neurochemistry articles are not terms that the public is familiar with. One term that is familiar to most is dopamine. Dopamine is an important neurotransmitter found in the brain, sending signals from one nerve cell to another, which in turn controls physical movement, memory, alertness, attention, emotions, and perceptions. In order to work, dopamine binds to receptors, not-so-surprisingly called dopamine receptors. There are multiple kinds of dopamine receptors and the one that this article focuses on are D2 dopamine receptors. Recently, these receptors have been noted as acting in a certain pathway, and the effects of this pathway on different brain disorders were noted.
The pathway that this article focuses on is the Akt/GSK3 signaling cascade. Like most other things in the brain, it is vital that this pathway is functioning at the right levels, having enough signaling, but not too much. Now, I could bore you with the nitty gritty, science-y details of what’s really going on here, but I’m not sure how helpful that would be. What is important to understand here is that this signaling cascade starts because dopamine binds to a D2 receptor. If levels of dopamine are off, or something goes wrong in this pathway, we are left with brain disorders such as schizophrenia, bipolar disorder, and Parkinson’s disease. This is why we care. The implication that disruptions in this pathway lead to these disorders is fairly new research, and by understanding exactly how this pathway works may lead scientists to discover helpful treatments.
Scientists are far from understanding everything about dopamine and the Akt/GSK3 pathway, but what is important to know is that current research is helping us get there. The complications come in when you realize that both dopamine and the Akt/GSK3 pathway do MANY things throughout the brain besides act in ways that affect these disorders. Thus if you are trying to target something in this pathway to help a specific aspect of a certain disorder, this could cause many unwanted side affects. The field of science and medicine has come a long way, but it has a long way to go! It is exciting to know that we understand more and more every day and this knowledge is helping discover new treatments of neuropsychiatric disorders.
Breaking the Stigma: Marijuana and the Endocannabinoid System
A couple of weeks ago I was talking to my parents and they asked me about classes and how they were going. I began to tell them about what I’m studying and began to talk a bit about neurochemistry. I told them about how we read an article each week and really break it down in order to fully understand what the article is talking about. I told them about how we’ve talked about insulin, dopamine and even endocannabinoids. Jokingly, my dad immediately asked,
“Endocannabinoids? You’re not going to start smoking pot are you?”
Although I know my dad was only kidding, his quick response when I said I was learning about endocannabinoids was not surprising. Although marijuana is associated with sitting on the coach, playing video games and raiding the house for food, there are enormous benefits to the drug that it seems few recognize, or at least take seriously. Cannabis has become an increasingly popular topic in today’s society, especially since there are states that have begun to legalize it for medicinal use, and for good reason.
I’m sure many of you have heard of THC, the main psychoactive ingredient in marijuana. But what I do not believe many know is that our bodies create similar molecules known as endocannabinoids. The two most important are anandamide (AEA) and N-arachidonoyldopamine (2-AG). These endocannabinoids do not have the same psychoactive effects, but do have very positive influences on our bodies.
The endocannabinoid pathway is very unique because it works backwards. Other pathways work from a pre-synaptic cell (cell sending the signal) to the post-synaptic cell (cell receiving the signal). The endocannabinoid pathway works instead from post-synaptic to pre-synaptic. This process is called retrograde signaling. Retrograde signaling is a feedback mechanism used to regulate chemical neurotransmission.
Manipulation of the cannabinoid pathway may provide treatment for those suffering from Alzheimer’s disease (AD). Cannabinoids have been seen to reduce oxidative stress, neuroinflammation and apoptosis (cell death) that are evoked by β-amyloid, which is involved in AD. Cannabinoids also may have the ability to promote repair mechanisms within the brain. Manipulating the endocannabinoid system in AD patients may offer a better substitute for current treatments that often have unwanted side effects such as liver damage and gastrointestinal disturbances.
More and more people are becoming aware of the positive effects of marijuana. But the main issue for many is its psychoactive side effects. Now researchers are working on ways to extract THC and use it in clinical trials. Scientists are also working on ways to decrease those psychoactive side effects in order to provide a more ethical way to administer treatment with the use of cannabinoids.
I understand why it is so difficult to accept that marijuana is good for you, especially with its psychoactive effects and the stigma that has been pressed upon it. However, with new methods of research and the vast amount of information there is out there, it is hard to ignore the facts. There is little evidence that smoking weed is bad for you. In fact, there is more evidence that consuming alcohol is more detrimental to our brains than getting high!
Now, I don’t mean that we should all start getting high while listening to the newest Arctic Monkeys album, but rather to open our minds to the reality that Cannabis can be good for the body. It can be beneficial for those suffering from Alzheimer’s, Multiple Sclerosis, severe pain, Tourette’s syndrome, seizures, migraines; the list goes on and on. Hopefully, as time proceeds others will begin to recognize its benefits, and work to focus on finding a way to harness its helpful properties.
Why are we a little shaky on Parkinson's disease?
Parkinson’s disease (PD) is a degenerative disease of the central nervous system that affect an estimated one million individuals in the united states. It has extremely visible characteristics such as uncontrollable shaking, rigidity, and impaired motor skills. PD is primarily a result of the death of dopamine producing cells in the brain. A protein called alpha-synuclin that normally mediates cell death is disrupted and leads to Lewey body formation in the brain.
There are several current treatments that attempt to counteract the effects exhibited by an individual with PD, but none fully rid the individual of the disease. The role of iron homeostasis in the brain in relation to the development to Parkinson’s disease has been under more and more investigation in recent studies of the disease.
Iron is carefully regulated in the brain and the imbalance of iron can lead to very disruptive consequences the central nervous system. Specifically, the role of iron chelators have been examined as a potential treatment for PD. Iron chelators work to bind iron and remove them from your system. A patient with PD exhibits elevated accumulation of alpha-synuclin as well as increased oxidative stress. Oxidative stress greatly contributes to mitochondrial dysfunction and neuronal death. These iron chelators have been found to inhibit these harmful processes from occurring. In particular, a drug named M30 is being studied as a potential treatment for PD. However, you can find sources of iron chelators in naturally occurring substances as well, such as green tea. Epigallocatechin gallate (EGCG) is abundant in green tea can help alleviate problems caused by increased iron overload as well as acting as an effective antioxidant to deal with the oxidative stress caused by PD.
Although there is no one-stop-cure-all method to preventing or treating Parkinson’s disease, there are things we know about the pathology that may provide useful insight in helping prevent the disease. The accumulation of iron and the resulting oxidative stress in your cells has been shown to contribute to PD. So taking healthy supplements that have antioxidative characteristics is extremely healthy (antioxidants play a role in a variety of diseases), as well as watching your iron intake and being mindful of what you’re ingesting into your body. Time and time again, diet seems to play a crucial role in our health and the prevention of a variety of different diseases.
Searching for a Solution
Lithium has been used to help treat a variety of mental disorders. The pathway lithium takes to help keep cells from undergoing apoptosis involves many factors. The involvement of lithium has a positive influence for diseases such as Alzheimer’s, Parkinson’s disease, as well as schizophrenia, bipolar, and depression. However, lithium is used differently in certain types of neurodegenerative diseases. For bipolar disease it is used to help with the manic stages, and with diseases such as schizophrenia, it helps with the depressive side of the illness. I found this to be particularly interesting in that it can help with both extreme mental stages, and helps to return the brain to a “normal” functioning level. Also, for many of these illnesses, when taking lithium as a medication, it is used in conjunction with other pharmaceutical drugs. I would assume this is to keep patients from over compensating in one direction, and if lithium is taken for depression, without other drugs it may cause the patient to have manic episodes.
As many drugs do, lithium is involved in deactivating the GSK-3 pathway. As we have learned before, this pathway is involved in so many functions within the brain. My thought is that there has to be some reason the GSK-3 pathway is in our brain, and even if we keep targeting it, there is bound to be some not so good side-effects from these drugs. There has to be a reason why lithium is not naturally made within the body, and that goes for many of the other pharmaceuticals that are prescribed. Yes, the GSK-3 activated pathway leads to apoptosis, or cell death, but it has to be involved in something that benefits our brain, or else it would not have been made. Same goes for p53. It helps keep cancer cells from forming, and by using lithium, p53 is essentially deactivated via the GSK-3 pathway.
The scientists who are involved in all of these long term studies for many of the medication for neurodegenerative diseases, I believe at least, are going to be finding some very interesting information. With all the unnatural things we put into our body, it is bound to backfire at least a little bit. When we evolved into what we are today, there has to be a purpose for whatever is in us, or at least there was, and if we keep adding substances that are not natural, the findings are going to be very interesting.
I believe that lithium is a wonderful treatment for people who are willing to try anything to help them feel better now, and are not concerned about the later (for some people there might not be a later if the now isn’t fixed promptly). We can only test, retest, and test again to see how our hypotheses actually affect people, and until we are certain how different chemicals act within our body, I believe it is only a measure that should be taken in desperate measures. As I have said before, we have become a society that just wants to have everything fixed right now, but what if we were to take the time to actually look at what is cause the diseases in the first place instead of always looking for a cure?