Neurochem in a Nutshell
Well, that’s just about impossible. I learned so much information this semester that it would be inconceivable to remember all of it. Many of the particular details and acronyms of important signaling molecules elude me as I look back on the semester, but that doesn’t mean the class didn’t teach me anything. I learned that phosphorylation is a process the brain and body rely heavily upon, that inhibitors can be great activators when stopping the action of other inhibitors, and that the brain is incredibly plastic and adaptable. I learned a ton of signaling pathways including cascades that release hormones, activate gene transcription, and alter metabolism. These are just a few of the lessons that come to mind and reflect the complexity of the brain. However, this is just the tip of how this class was useful
Information is Good – Applicability is Better
The real triumph of this capstone is the real life experience it gives in interpreting and explaining scientific studies. These blogs have been a great way to practice simplifying complex neurological phenomena without using a lot of inaccessible jargon, yet not losing the validity of the information in the process. It also gave me plenty of chances to find gaps in my own understanding and the opportunity to fill them. The class had an interesting and fairly novel way of filling the gaps in knowledge that I appreciate. By allowing the class to investigate the topics within articles that were confusing or lacking, it provided each of us a chance to learn far more through cooperation. Wednesdays, when each student would present his or her chosen topic of the week, were packed with useful information that added clarity and relevance to the articles.
Neurochem is Educational, Enjoyable and Other E words
Lastly, the class made neurochemistry fun and entertaining. I always felt like the discussion on Fridays always made the topics important to my life. They provided context to hypotheses and data that would otherwise likely be unexciting to me. The issues that were brought up each week revolved around controversy and current events that made even the most dry and dense of articles worthwhile. The time and energy I put into the course were more than repaid by the edification and expertise I got out. In summery, the class gave me three E’s that every college course should provide the students that take them: education, experience, and entertainment.
Alcohol – Inhibition to the Point of Activity
It’s Five O’clock Somewhere
And even if it wasn’t it probably wouldn’t stop many people from drinking. Alcohol abuse and dependence are global health issues and in the United States they affect about 14 million people. The article we read on the ethanol (alcohol) also describes that there are few choices for treatment alcohol use disorders. One reason for this is likely that the action of alcohol on the brain is not well understood. However, the article seeks to offer some possible mechanisms for the interesting ways alcohol changes cognition and behavior.
Is This an Off Switch or Not?
Alcohol has an interesting way of inhibiting particular parts of the brain, while activating others. Ethanol increases the firing rate of dopamine neurons, which play an important role in the reward pathway in the brain, yet it inhibits other neural elements known as NMDA receptors, which are another important actor in ethanol’s rewarding effects in the brain. How can this be? Interestingly, the extra dopamine firing leads to an inactivation of a molecule, called pp-1, that usually helps to shut off NMDA receptors after they’ve been activated. In other words, even though NMDA receptors have decreased action when affected by ethanol, they also have increased action because they aren’t being turned off by pp-1. It turns out that during this interaction the effect of inactivated pp-1 is larger than ethanol. Meaning that NMDA receptors aren’t inhibited much by ethanol despite its direct effect on the receptors. This is exhibited by mice that are lacking a crucial element in the pathway to inactivate pp-1, known as DARPP-32, show less ethanol self-administration than mice with DARPP-32. This is evidence that increased dopamine and NMDA receptor activity are likely important to alcohol dependence in humans as well.
Ethanol’s Big Effects – Perhaps Due to Tiny Interactions
The other interesting effect of ethanol I’m going to talk about is its incorporation into the cells of the body. An enzyme known as PLD is important to the incorporation of ethanol into the body cells. Normally this enzyme acts to produce a molecule, phosphatidic acid, which acts to relay signals to important cellular proteins. However, in the presence of ethanol, PLD would much rather hang out with ethanol and convert it into PEth so that it fits into cell membranes, which are barriers around the cells that act to keep out certain materials and letting in other. When PEth is incorporated into cell membranes it increase the rate at which ethanol can enter the cell and prevents phosphatidic acid from relaying its signal to the proteins within the cell. Both of these actions act to change cellular function and it is suggested that one of the two or both may lead to increased alcohol tolerance. Unfortunately, both alcohol tolerance and alcohol dependence have very limited options for pharmacological treatment. As usual, the best way to solve this problem is continued research and discussion. Every new discovery leads to possible solutions to issues facing many people locally and abroad.
You Booze, You Lose
It’s fewer than two weeks away from Christmas—time for get-togethers, holiday parties, and family gatherings. What’s a better way to warm up from the chill and snow than having a nice holiday drink?
It’s no surprise, then, that rates of drinking spike sharply around Christmas. This has been linked to more alcohol-related car crashes and violence around the holidays. So it’s a good idea to keep in mind how alcohol affects your body, and what a good limit for your drinking is.
We recently discussed in neurochemistry how alcohol affects the body, particularly the signaling processes in the brain. After alcohol is ingested, a chemical called gamma-aminobutyric acid GABA is released in the brain. The primary effect of GABA is to reduce the activity of cells in the brain. As the brain activity is reduced, a person feels more laid back, comfortable, and relaxed.
GABA “inhibits” the usual high activity of the brain by blocking the effect of another chemical called glutamate. Glutamate causes the neurons of the brain to fire and send signals. GABA inhibits the activity of these neurons, causing decreased activity in the brain. This is why some cognitive functions are impaired during alcohol use, specifically memory. GABA affects glutamate receptors, which are important for encoding memories. This leads to impaired memory ability and “gaps in memory.
This “relaxant” effect of alcohol is a large part of what causes people to continue using alcohol. For some people, it makes social interaction easier. For others, it makes socializing more enjoyable through the “buzz” created by alcohol. Many others just enjoy being able to relax after a hard week. However, as we know, past a certain level, the effects of alcohol become more negative and not as enjoyable. The impairment from GABA causes dizziness, slurred speech, and poor coordination. Nausea and vomiting may occur as well. This two-part effect of alcohol has been called the “biphasic effect,” since its positive results come before some its more negative aftereffects.
After continued use of alcohol, tolerance can develop. This means that the body has become accustomed to the alcohol in the system and now can counteract the impairment. Glutamate becomes more active, overpowering the inhibitory effect of GABA. How does this happen? There’s evidence that several different chemicals and molecules in the brain are involved in reversing glutamate receptors desensitivity caused by GABA. One molecule called Fyn is important for cellular structures in the brain and seems to be involved in this process. It interacts with glutamate receptors and change their shape so that they become more active. Increased activity of glutamate means less effects of alcohol on the brain.
When a person becomes more tolerant to alcohol, this can impact their drinking habits. First of all, when someone becomes “used” to alcohol, he or she will be more likely to drink more to get the same effect. Thus, they are at greater risk of inadvertently drinking a toxic amount of alcohol. 
Additionally, when a person becomes tolerant, there is evidence from animal studies showing that part of tolerance is due to the environment they are used to drinking in. For example, a person might develop alcohol tolerance from typically drinking with friends in a club on Friday night. In this case, being in the club will help produce their reduced response (high GABA activity) to alcohol, leading them to increase their alcohol intake. But if they try to drink a similar large amount of alcohol in a different environment, their tolerance may be reduced from being in a different environment. This dose may overpower their system, resulting in possible harm.
Alcohol’s effects, then, are more complicated than GABA’s relaxing effects on the body and inhibitory action on chemicals like glutamate. Instead, your drinking habits and experiences shape how your body and brain respond to alcohol. Keep those in mind as you celebrate this holiday season!
Drunken words are honest thoughts.
Alcoholism is a serious problem around the world and especially in the U.S. Alcoholism affects some 14 million people in the United States alone, costing $ 184 billion a year (Newton &Messing, 2006). Heavy drinkers are also more susceptible to cancer than those who drink on occasion or not at all. This very common substance in our society was once illegal. But in the present day, it is very much legal to those of age and there are no restrictions on how much one individual can buy. The types and proofs of alcohol available for purchase can contain up to 80% alcohol!
Have you ever wondered why alcoholic beverages are also referred to as “spirits”? The mechanisms of alcohol in the brain work in a way that inhibits our inhibitions. Our inhibitions are those that restrain us from being inappropriate in public, speaking out of turn and the way we talk to each other. What I mean by this is that when people are inebriated, they act differently than if they were sober (obviously). But how does this happen?
Alcohol is substance that brings individuals a sense of unwinding and relaxation. In other instances it is used for celebrating and partying. I am often told by my fellow foreign exchange students that alcoholic beverages are abused in the U.S. unlike European countries; it is safe to say that alcohol could be a drug of abuse. When we imbibe, we are activating the reward center of our brain which is mediated by dopamine. Dopamine continues to activate neurons in the central nervous system called glutamate receptors that counterbalance inhibition by alcohol. The release of opioids in the brain, caused by alcohol, trigger a cascade of GABA release, which is an inhibitory neurotransmitter and is vital in inhibiting dopamine neurons. This also causes our decision making and response time to decrease. Have you ever heard of someone being called an emotional drunk? Alcohol plays a large role in emotion as we can see by the inhibition of inhibitions. But when alcohol is consumed regularly, substance dependence can eventually form due to the activation of the pleasure/reward system. The substance (alcohol) is usually the beginning of addiction. But when actions of drinking start to become habitual, the motion and/or holding the beverage become a fixation to the individual.
I’m not trying to insist that alcohol is the root of all evil and that anyone who consumes it will become an alcoholic. It is actually a fact that occasional ingestion of such libations is good for the body and heart. But when it becomes apparent to us that someone that we care about is abusing this substance, should we do something about it? Or should we let them handle it themselves?
http://www.alcohol-facts.net/
Leptin's Other Personality
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.