As we have seen from studying different neurological diseases and drug mechanism, neurotransmitters play crucial roles in bodily processes that we normally overlook. Leptin and insulin are two transmitters that control energy homeostasis and keep our weight and food intake in balance. The increase of uptake of high fructose corn syrup disrupts the natural processes involved with insulin and leptin, which can lead to, increased tolerance in both. Leptin also has a vital role in reproduction that accompanies its role in energy homeostasis.
In the endocrine system, leptin regulates key hormones that allow for the production of gametes. When leptin levels are askew from improper diet, whether it is obesity or anorexia, leptin is not able to play its role in the endocrine system. Too much leptin cause by over eating or leptin resistance can cause irregular menstrual cycles in women, early onset puberty, and the inhibition of production of testosterone on males. A deficiency in leptin can lead to a halt in the production of gametes, and an improper environment or gestation in females.
Leptin’s role in reproduction seems to be a safe guard for pregnancy. In that if the suitable amount of food is not available, conception is less likely to happen. Having this safe guard prevents harm to offspring and the mother because if there is not a suitable amount of food available, there is a less likely chance that the offspring will survive which would lead to a waste of what little resources are available.
Root of Emotions
Emotions and mood are a small part of the human life, but are complex in the way they are controlled and stimulated. Bipolar disorder seems to be a malfunction in the control of these two processes that is characterized by continual changes in mood, cycling between manic and depressive phases, along with poor control of temper. One way to treat the symptoms of bipolar is to use mood stabilizers to level out the highs and lows and people with bipolar disorder go through. It is believed that these symptoms arise from an imbalance of neurotransmission, consisting of excessive dopaminergic and glutamatergic transmission along with reduced cholinergic muscarinic transmission, and that mood stabilizers attempt to restore proper transmission. Arachodonic acid has become a molecule of interest when looking at mood stabilizing. Arachodonic Acid (AA), is an abundant fatty acid in the brain which helps maintain hippocampal cell membrane fluidity and helps protect the brain from oxidative stress.
Mood stabilizers may be a good solution to cover up the symptoms of bipolar disorder but this idea seems to stop short of the real problem. Some where in the brain, the production, synthesis, reuptake, or release of the neurotransmitters identified above is askew. I believe instead of masking the symptoms of bipolar, researchers should look more into where this imbalance is coming from. In doing this, it would help cure almost all cases of bipolar because the brain could be set to normal settings of these essential neurotransmitters.
Alcohol : Why are we addicted to it?
Alcoholism is one of the serious addiction problems that we are facing today. Data state that alcoholism affect some 14 million people in the United States alone, costing US$ 184 billion a year. (Newton &Messing, 2006) Why are some of us addicted to alcohol and why is alcohol a part of our society? Alcohol plays a big role as a mediating agent among social interactions today. The amount, frequency and subsequent magnitude of impact on the individuals vary as the reasons for drinking varies. In this blog, I will focus on the addictive potential, withdrawal symptoms of alcohol as well as the current therapeutic targets.
Dopamine is the major neurotransmitter in the brain that induces feelings of reward and reinforcement. Alcohol increases the neural firing of dopamine neurons in the ventral tegmental region of the brain. This activation in turn causes increases increase release of dopamine in the nucleus accumbens, a region in the brain that is rich in dopaminergic neurons. Along this signal transduction cascade, this dopamine activates a particular type of neurons called DARPP-32 which increases the level of glutamatergic NMDA receptors which counteracts the inhibition of receptor function by alcohol of the neurons. Hence, DARPP-32 neurons are important in facilitating rewarding feelings of alcohol. Alcohol also induces addictive effects through the mesolimbic pathway which involves amygdala, a brain region that regulates emotions, in the brain which is involved in dopamine-induced pleasurable feelings. Alcohol induces increase release of opioids (e.g. beta endorphins) in the brain and these opioids inhibit the inhibition of dopamine neurons by GABA (gamma-amino-butyric-acid) which is a major inhibitory system of neural actions in the brain. Hence, alcohol induces addiction similar to that of nicotine and opioid drugs.
The most challenging aspect of treating alcohol and drug addiction is the relapsing course of these disorders. Although substitution therapies for nicotine and opioid dependence have proven to be relatively effective, there is a need for new pharmacotherapies designed to decrease the frequency and severity of relapse. NMDA receptor antagonists are one of the targets for treatment of alcohol addiction since blocking the action of the NMDA receptor can block the increase dopamine release and dopamine-related feelings of reward. MK-801 is one of the widely used NMDA receptor antagonists in treatment of alcoholism.
According to the article ‘Treatment of Alcohol Withdrawal’ by Myrick.et.al, withdrawal symptoms of alcohol include headache, tremor, sweating, agitation, anxiety and irritability, nausea and vomiting, heightened sensitivity to light and sound, disorientation, difficulty concentrating, and, in more serious cases, transient hallucinations.. Patients with alcohol withdrawal should be subject to a physical examination, with particular emphasis on detecting conditions such as irregular heartbeat (i.e., arrhythmia), inadequate heart function (i.e., congestive heart failure), liver disease (e.g., alcoholic hepatitis), pancreatic disease (i.e., alcoholic pancreatitis), infectious diseases (e.g., tuberculosis), bleeding within the digestive system, and nervous system impairment. Vital signs (e.g., heartbeat and blood pressure) should be stabilized and disturbances of water and nutritional balances corrected. (Myrick.et.al, 1998)
Great Capstone
I think that this class was a great way to cap off my undergraduate college career and is a great capstone for most science majors. I was able to develop better ways to analyze articles and studies, and be able to think critically about them. The discussions were very beneficial to fully understanding the articles because perspectives from different majors were being mixed together. I really enjoyed how chemistry majors could inform others more about the biochem aspect while psychology majors could inform about the mental aspects. This mixture of different types of scientist in training allowed for a further understanding of the material. Learning about the different neurological diseases and drugs gave me a further understanding of the human brain, and just how complex it really is.
Alcoholism Starting Point
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While millions of Americans use alcohol as a social lubricant, many cross the line of recreation use to addiction. Whether we like it or not alcohol is a drug, but because it is so socially acceptable, its reputation and regulation is much different compared to other drugs. The negative effect it has on society is overshadowed by the positive stigma it carries today. In moderation it can be a good thing, but from an early age kids are taught that alcohol is bad, but kids are never taught how to properly and responsibly use alcohol. So instead, teenagers want to be rebellious (imagine that), and try something they have always been told to stay away from. This can lead to abuse of alcohol because they don’t know how to use in moderation. By abusing alcohol at such a young age, teenagers manipulate their growing brain to be used to binge drinking, which can develop into dependency later in life.
When ethanol is present in the brain, it alters the communication processes that are happening between nerves and within the nerves by interacting with receptors and altering intracellular signal cascades. It does this by inhibiting excitatory activity and increases inhibitory neurotransmissions. The pathways that are affected from the presence of ethanol can provide and underlying mechanism for the addiction that the chronic use of alcohol can lead to. The primary effect of alcohol in the brain is the increase of the stimulation of the GABA receptors, which cause a depression in the central nervous system. As alcohol abuse continues, these receptors are desensitized and down regulated. Which results in tolerance to alcohol and also physical dependence. Starting this cycle at an earlier age, along with irresponsible consumption may lead to a higher potential for physical dependence.
Too Much of a Good Thing
Obesity – It’s not just for the Wealthy Anymore
I don’t need any statistics to convince you that obesity is a problem in America. On evening news shows there are frequent segments concerned with the recent rise of obesity, often focusing on the growing rate of childhood obesity. In 2003, the surgeon general named obesity “the fastest-growing cause of disease and death in America,” and it hasn’t slowed down any since then. The article we read in class called it an urgent health issue and hoped that some of the research it presented and hypotheses it put forward might lead to further research leading to more effective and practical forms of obesity treatment.
Insulin and Leptin – the Dynamic Duo
After eating a large meal, there are a number of processes that should begin to properly utilize and store the food that was just consumed. Many of these processes are directed by the action of leptin and insulin acting cooperatively. Insulin signals cells to take up glucose from the bloodstream and either use it as energy or store it as glycogen. Leptin, on the other hand, plays a crucial role in telling the brain that enough food has been consumed and acts as an indicator of energy balance. When insulin control fails the result is diabetes, which prevent effective insulin signaling and allows blood-glucose levels to increase to toxic levels. A failure in leptin signaling leads to uncontrolled appetite and usually obesity.
Insulin and leptin act in part by activating neurons in the hypothalamus that express proopiomelanocortin, which release a neuropeptide that tells the brain to reduce food intake and increase energy expenditure. Alternatively, they prevent the activation of another type of neuron in the hypothalamus that signals the body to promote food intake and decrease energy expenditure.
Too Much of a Good Thing
Why are these hormones failing in the modern diet? In the modern world the cheapest food, which often also tastes pretty good because of high-fructose corn syrup, is highly processed. This means it is packed full of calories, fat and plenty of other nonsense, literally (read the ingredients on a pack of candy or a bag of chips and tell me how many food products you recognize from your kitchen). The types and the amounts of the foods we eat are stupefying our bodies ability to sense satiation and undergo properly metabolism. Studies described in our article have shown that high fat diets can lead to insulin-resistance, while consistently high levels of leptin, likely from overeating three times a day and filling in the meantime with snacks, leads to leptin-resistance. When the body becomes resistant to these hormones it no longer realizes when enough food has been eaten and has a hard time properly utilizing normal quantities of food, much less the extra portions added on from the lacking brain-to-body signals. Fructose, a sugar that makes up about half of high-fructose corn syrup, has also been blamed for leptin resistance.
The Frosting on the Cake
Maybe in this case I should say the low-fat ranch dressing on the baby-carrots. Although obesity is a huge problem it is also largely preventable. Reducing food intake and exercise are old standbys to combat obesity. The article mentions that keeping a low calorie diet can increase levels of leptin in the blood thus helping the body to be satiated after less food. This means that if a diet is stuck with long enough it should become easier and easier as time passes. However, diet and exercise are not easy in a fast paced world like the one we currently find ourselves in. This is where further research into the action of leptin and insulin may come to the rescue. By better understanding how these hormones affect appetite and metabolism, new treatments may become available to help get the jump on obesity and create a healthier modern world.
Opinions of sciences
When you see this picture what do you think of? This is the molecule thimerosal, a mercury containing compound that is a central in the mercury vs. autism debate. I will admit that I am a new to this controversy, but that doesn’t mean I can’t have an opinion. As Jeffrey P. Baker points out in his paper Mercury, Vaccines, and Autism (2008) the current mercury debate is heavily intertwined with historical opinions. To be honest I also rely on these historical opinions which are often incorrect and based off of pseudo science. This can be dangerous because pseudo science spreads like wild fire. The difficult part with this is that most current events are curent events because they are not understood. This means often scientists are still trying to figure what is right and what is wrong, so there will not be unified positions. Scientists can also be quite opinionated when it comes to what is right, and generally it biased in terms of their research.
How is the general public suppose to know what is right and wrong then? Medicine may be destroying our babies, birds now have a flu that could kill everybody, neutrinos now go faster then the speed of light. We live in a world of pseudo science, and a lightning fast information system. I think we need to slow down. We want instant results for everything including research. But we all have to realize it takes time. Once a professor told me “However long you expect an chemical experiment/research to take, multiply that by 6”. It takes time, it takes time. So my advice would be, if some sort of scientific breakthrough is announced take it with a grain of salt, scientists can sometimes over-exaggerate the implications of their work.
So it has been a while since the peak of the moms against mercury, it could be said that the smoke has cleared. So what is the scientific opinion on thimerosal at the moment? Aforementioned Jeffrey P. Baker has written a paper on thimerosal, and he does a very good job taking a holistic look. First he mentions that people not lived through the disasters that these vaccines are preventing. Just keeping the terribleness of these diseases in mind it may be enough to give vaccines another chance. He first looks at why mercury was included in the vaccines. Mercury was seen as a way of destroying the risk of contaminated vaccines which in one instance killed as many as 21 children.
Baker then goes on to mention that another problem in the misunderstanding of thimerosal is “the convergence of the history of ethylmercury with the parallel history of methylmercury in the mid-1990s.” Methelmercury being proven to be somewhat toxic which people are comparing to the ethylmercury which is found in thimerosal.
These molecules may look very simular there are only one methyl (CH3) group apart. This may be part of the reason the opposition groups get confused. It would seem that two molecules that are so close in structure must have simular effects. Aka because methylmercurys are bad for you ethylmercurys must be too. The funny comparison I would suggest would be the methlymercury/ethylmercury relation compared to the testosterone/esteriol (male and female hormones respectively) relation. Just as methylmercury/ethylmercury differ by one methly group so do testosterone/esteriol showing that the difference in methly group can create quite different results.
As always the body is much to complicated for me to talk about, let alone understand. Take the scientific world with a grain of salt.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376879/?tool=pmcentrez
Things I learned…
The final blog. I can’t believe the semester is over. It doesn’t seem real – there isn’t even snow on the ground. I would like to end my semester with one last blog about some things I learned in neurochem.
The brain is cool.
This semester, our class delved into the complexities of the human brain. As a biology/chemistry student who had never had a neuroscience class, a class about the brain seemed pretty daunting. However, after doing much research, reading many papers, and being taught by my neuroscience-loving classmates, I feel much more comfortable talking about this crazy organ. It seems completely unfathomable and amazing to me that our brains can do the complex things they do – using chemistry. It’s awesome.
Scientists are cool.
This leads me to another thing Neurochemistry has taught me – it’s fun to get together with scientists and talk about science. We are nerdy and awesome people. This class was especially interesting because people from so many areas took this class – neuroscience, psychology, biology, chemistry, philosophy. I think our different backgrounds really brought a diversity of information and topics to the table which really enriched my experience. Getting together and talking about science is fun.
The brain is an unsolved mystery.
Who knew that so many disorders and diseases concerning the brain are still uncharted territory?! Before this class, I would have thought that scientists would have already figured out the exact mechanisms of things like autism, Alzheimer’s, ADHD, bipolar, smoking, schizophrenia, Parkinson’s, migraines, and the effects of drugs like opioids and alcohol. However, this isn’t the case! There are still so many mysteries concerning the brain which makes reading papers in Neurochemistry so exciting.
Everyone is a little messed up.
What is normal anymore? Neurochemistry class taught me that the “normal” brain seems to be nonexistent. We asked repeatedly every week – what if we knew everything about the brain so that we could just give everyone their set of drugs and everyone would be perfect? Would we all be the same? Would you want to change? We also learned that our environment is important and that our parents probably had a hand in messing us up a little bit. Thanks Mom and Dad.
That’s about it. Neurochemistry has been a really awesome class. Merry Christmas!
Backward Logic and Bipolar
FLASHBACK!!!
Five years ago you would find a 17-year-old version of myself sitting in my high school chemistry room. I felt like the king of the world, I thought I knew everything there was to know about chemistry and the world around me. In all honesty I thought the noble prize in chemistry just a reward for chemists who found some new use for chemistry. And there is no way I could have been anymore wrong. I think there is more unknown then there is known, and this weeks article on bipolar disorder brings this to light. The Article is titled “Bipolar disorder and the mechanisms of action of mood stabilizers”
This article looks at four different drugs called mood stabilizers that are used to “treat” bipolar disorder. In todays world researchers study chemical pathways of a disorder and decide where they should “attack” the disorder to stop it. They then create the medicine that does just that! Problem solved. Bipolar is different, over time we have found medication that accomplishes what we want (kind of). These drugs are termed mood stabilizers. The odd thing is we know that these drugs work, we just don’t know how. So the thought is that researchers are going to work backwards. The “cure” is known so we just need to find out what exactly it “cures”.
To quote S. Sobo “How can we argue that we are treating […bipolar disorder…] at a fundamental, etiological level of the illness when we don’t know what the chemical problem is?
So researchers have ideas on how bipolar disorder may happen, but it is still very hypothetical. A few years ago there was a hypotheses called Myo-Inositol Depletion, which was believed to explain bipolar disorder. But in just 5 years researchers have discovered that this hypothesis isn’t probable. This weeks article we read instead focused on the arachidonic acid cascade.
To go into specifics a bit more there are 4 main drugs used to null bipolar symptoms: Lithium, Carbamazepine, Valproic acid, and Lamotrigine. So when we look at a system like the arachidonic acid cascade we try to find how this causes the problem (bi-polar) and then how the drugs prevent this from happening. One way this can be done is by finding specific points in the chemical cascade and finding how drugs affect that point. After all this data is collected we can step back and try to take a holistic view of the disease.
So it can be seen that the arachidonic acid (AA) cascade can cause neuronal damage in quite a few ways. So if we can at what points the drugs stop the AA pathway from proceeding forward we can understand how bipolar disease works. The paper the class was assigned to read actually has a nice spreadsheet breaking down all of the elements of the AA pathway and how the drugs affect these specific elements. On complication to this process is that some of these drugs help some people but not others, at the same time these drugs have different effects on the specific parts to the pathway. For example all four drugs lower COX-2 levels. Whereas COX-1 levels are only lowered by Sodium valproate, the other drugs having no effect. Everything is so complicated…
Take home message the body is complicated, and it is even more complicated finding out why things go wrong. Also I think the general public should know that doctors/humans just don’t know everything.
Addiction or Pain?
Severe pain affects approximately 6% of the population at any given time. This pain can come from nearly any source and may be dealt with in various ways. One way in which severe pain is moderated is through the use of opioids. Opioids are analgesics (painkillers) which decrease the perception of pain, decrease reaction to pain and increase pain tolerance. However, opioids are also commonly taken recreationally due to their ability to produce feelings of euphoria.
Although the significant pain relieving effects, and maybe even the euphoria, sound great there are many issues with opioid use. Chronic use of opioids is associated with tolerance as well as both physical and psychological dependence. Due to this, medicinal opioid use is quite limited and much research has been conducted to explore the negative effects of the drug.
Addictive drugs, such as opioids, act via dopamine pathways and more recently have been associated with glutamate as well. Both of these neurotransmitters are found in various regions throughout the brain and play various roles in the process of addiction. Dopamine is largely related to the reward system which tells a drug user that the drug is ‘good’. Glutamate has been linked to the seeking behavior of a drug addict and withdrawal behaviors which may result in relapse. When opioids bind to receptors in the brain they activate the reward pathways and their effects as well as cause the release of glutamate and activate its receptors. This then initiates the addiction process after continuous use.
So the question is, is it really that bad to be addicted to opioids if it relieves your pain? Well, unfortunately chronic opioid use has many adverse side effects outside of addiction such as depression, confusion, hallucinations, bradycardia and tachycardia. For those who do suffer chronic, severe pain however, these side effects may seem like a simple trade off compared to what they are currently experiencing.