Neuroscience is a fairly new frontier in the scientific world. It combines biology, chemistry, psychology and other fields at the specific point of the nervous system. These interactions and their implications in the human mind are fascinating. I became so interested in neuroscience specifically for the reason that it encompassed my diverse interest in various fields of science.
Neurochemistry has been one of the most intriguing courses I have taken at Concordia. It has pushed me deeper into the world of neuroscience and into a more specific and concentrated area of it. Understanding how all of the things I learned in general chemistry, organic chemistry and biochemistry apply to our brains has been very rewarding – it is always nice to realize that what you learn in class really does apply to the real world.
The articles we read were hot topics in the world of health and diseases such as Autism, Bipolar Disorder, Cancer, Alcoholism, etc. They are huge issues currently affecting our society and currently unresolved. The articles make us evaluate what researchers have found and the validity of their conclusions based on other literature; they make us really think about what is happening in our brains and how all of these diseases are affecting that specific, and vitally important, part of our body.
I think that one of my favorite aspects of this capstone course is Friday discussions. Although we may get off topic from time to time, these discussions truly make us evaluate the issues our society is facing. It makes us apply the research to the real world and understand how it affects us and what it can lead us towards in the future. Is social media affecting multiple aspects of our life? Can you really cure alcoholism? Would everyone form cancer if they lived long enough? It makes us face questions such as these and evaluate our own lives as well.
I have also learned many valuable skills in this course related to reading scientific literature. We learn to carefully read the articles and organize them to initially understand the message the author is trying to send. We then tear through the paper and research items that we still do not understand. This teaches us how to search for credible sources and evaluate the validity of all of the information that is available to us. We then put all of this together to best understand the article and all that it can teach us. Finally, we use this information to discuss the ‘bigger picture’ and the implications it has in our lives and society in general.
Overall, neurochemistry was a great capstone course. I feel that it was a wonderful way to bring together all of the material I have learned in the chemistry field thus far at Concordia and to develop my skill sets as a scientist.
Is there a single cause of autism?
This week’s article discussed a new hypothesis for the cause of autism. It is called a redox/methylation hypothesis and suggests that environmental issues activate autism in individuals who are genetically predisposed to the condition. The hypothesis points a finger at heavy metals and xenobiotics (potentially harmful chemicals). However, it seems that if this were the case, autism levels should be lower now than they were in the past, which is not the case. National and worldwide government agencies have set increasingly more strict restrictions on the amount of heavy metals introduced to our environment. The hypothesis also mentions vaccines containing ethylmercury as a cause however, ethylmercury has been removed from vaccines and autism levels have only risen.
It seems that something else is playing a role in causing autism. The mother-child interactions both in-utero and once the child is born seem to be very important. It has been suggested that the mother’s attitude towards the fetus could be related. If the mother did not want the pregnancy or is unsure about her feelings towards the fetus, the fetus is not talked to as much and does not experience the same in-utero environment as a fetus whose mother truly desired the pregnancy.
Once a child is born their interactions with their mother are also crucial. If a child is not stimulated and given attention they may be at risk for difficulty with social interactions later in life. A child frequently left alone may become more independent and not desire interactions with others or not know how to properly interact with others. This seems to better trend with time and autism incident increase because mothers are more frequently going to work earlier and earlier after a child is born. A fairly average maternity leave may be as little as four weeks. After this point the child is likely taken to a child care facility of varying quality. With only a few adults per multiple children, a child is not getting as much attention as they would have say 75 years ago when many mothers did not work and stayed home with their children throughout their entire childhood.
Clearly the cause of autism still remains under investigation as no hypothesis seems to fully explain the disease. It is possible that many of the suggested hypotheses are working together as opposed to there being one single, easy answer.
Is a pharmacological cure for alcoholism in our future?
One of our recent articles discussed the effects of ethanol, or alcohol as it is more commonly referred to. Multiple signaling pathways in the brain are affected by alcohol either directly or indirectly. These affects change depending on the brain region and whether the ethanol exposure is acute or chronic. Based on the varying information provided by the article it seems that a pharmacological cure for alcoholism is far in our future. However, it raises many questions about the possibility of a drug to reverse the behavioral effects of alcohol or the possibility of an alcoholism drug.
What would be the advantage of creating a drug that would reverse the behavioral effects of acute alcohol use? What first comes to mind is use in emergency rooms for individuals who come in with alcohol poisoning. A drug could be created to reverse the effects of the alcohol and ‘sober them up’. However, if individuals experience this they may begin to think that they can drink as much alcohol as they want and all they have to do is go to the hospital and the doctor will reverse the effects with a simple injection or pill. Especially in the case of teenagers or young adults who do not yet understand the extent of the negative effects of alcohol on their bodies may abuse the creation of this drug.
Second, what aspect of alcoholism would a drug for chronic alcohol use target? Would it target the reward of the alcohol or the behavioral effects or tolerance or the drug-seeking behavior? Alcoholism is not a simple condition; there are many aspects. It seems that there would need to be a drug to encompass all of these aspects which may be unreasonable. Although, it seems that the single best area to target would be the desire to seek out alcohol. If the desire can be decreased then, in theory, the alcoholic would cease to seek out the alcohol and therefore no longer drink.
However, with the information from this article it seems that too many structures are involved with different effects from alcohol exposure to really create a successful drug. It is most likely that pharmacological ‘cures’ are a long way down the road and other options should be considered. For example, teaching children and teens about the extensive negative effects of alcohol use to prevent binge drinking and alcohol poisoning. Also, therapies or support groups such as Alcoholics Anonymous may be more helpful to chronic alcohol abusers. Individuals must have the desire to face their alcohol overuse and overcome the obstacles even though it may be a more grueling process.
Is Autism really on the rise?
This week’s article discussed a hypothesis surrounding the environmental and genetic factors that may contribute to the development of autism. From 1970 to 2002, the diagnosed cases of autism rose from 3 in 1000 to 66 in 1000, increasing over twenty fold. Naturally, a lot of research has gone into why these rates seem to be increasing so dramatically. To understand this, we need to understand what can potentially cause autism.
Neurological diseases or disorders are complex, and focusing in on a single neurological dysfunction is rarely possible. The complexity of our human brain often leads to multiple hypotheses on what causes each disease. While genetic factors play a role, there are environmental factors that can cause autism as well. While multiple theories for the causes of autism exist, our paper this week focused on the role of heavy metal toxicity and oxidative stress in facilitating its development. Heavy metals, such as cadmium, arsenic, lead, and mercury, can have profound effects on the brain even at small concentrations, being correlated with disorders like ADHD and autism, and even diseases like Parkinson’s and Alzheimer’s.
Heavy metal compounds can be referred to as xenobiotics, chemicals found in our body that are not produced or expected to be present in our biological system. Heavy metals can bind strongly to sulfur containing compounds in our bodies, disrupting normal paths of sulfur metabolism. Sulfur, through glutathione, methionine, and other molecules, plays an integral role in DNA methylation, which is important in gene regulation and other processes. Particularly, this metabolism is crucial during oxidative stress, thus metal’s interfering with this pathway can lead to general dysfunction, leading to symptoms that often characterize autism. For example, the body attempts to clear xenobiotics from the body by binding them to glutathione and clearing them in urine. Therefore, heavy metals can remove important sulfur-containing compounds from our bodies, leaving us more vulnerable to oxidative stress.
Can the actions of heavy metals explain the surge in cases of documented autism? If this was the case, we would have to expect rising levels of heavy metals being inadvertently consumed/entering the body. A well-known controversy surrounding heavy metals involved thiomersal, an ethylmercury-based preservative used to prevent bacterial infections, found in vaccines. Rising awareness of the deleterious effects of mercury in the 1970’s led to a well-publicized, fierce backlash against the vaccine. Despite extensive research among scientists declaring the concentrations of mercury in these vaccines were far below toxic levels, controversy still surrounds the compound, and it has been removed completely from vaccines. Its removal did not decrease the rising autism rates, reliably indicating it wasn’t a significant cause of autism. In addition, heavy metals are sometimes present in soil, while trace amounts of heavy metals can be found in certain cosmetics. These levels aren’t in themselves very dangerous, but regular usage is hypothesized to have possible side effects. Despite our possible exposure to heavy metals, little is known about whether exposure is increasing. In fact, increased awareness of the toxic effects of heavy metals has led to government agencies cutting back their usage. Thus, it is possible heavy metal exposure may even be decreasing, despite autism levels still rising.
What else could cause autism? A less chemical explanation is lack of proper social interaction. Studies have shown that babies who didn’t receive much touch from their parents or didn’t receive much attention in early childhood were at a greater risk for developing autism. In a society where it is becoming more likely for both parents to have jobs, it is possible children on average are receiving far less attention from their parents than children raised forty, or even ten years ago. This lack of social interaction could lend itself to the social problems that are displayed by autistic children. However, children who may not see their parents as often still may get plenty of social interaction at their daycare or school. Thus, it is possible this phenomenon isn’t a significant contributor. Because it is hard, even impossible, to provide reliable quantifiable data of this effect, it isn’t easy to cite this as a main cause of the surfacing epidemic.
It is possible that as scientists we are missing a universal factor lending itself to increasing levels of autism. Most likely, it is a random combination of factors leading to each autistic case. However, is it possible that cases of autism aren’t actually increasing? Awareness of autism is constantly increasing, which could lend heavily to the increased amount of documented cases. Cases that may have previously gone unnoticed forty years ago may be diagnosed readily in the current climate. Perhaps the “increasing levels” of autism is actually a marker of a good thing: children with autism being diagnosed more readily may receive positive treatment whereas a child in their same position decades ago may have gone unnoticed, which provides them a better chance to live normal, successful lives.
Most neurological disorders are as complicated as they are devastating. The etiology of current disorders like autism are often filled with hazy areas and judgment calls. While it may be difficult in the short run to develop a universal “cure” for autism or similar disorders, increasing awareness can help provide treatment for those in need. However, there is a fine line between increased awareness and trigger-happy diagnoses. Diagnosis with social disorder often comes with a stigma that may make the patients feel even more helpless. As we seek to find the scientific explanations of these disorders, it is important for us to treat each case with care and deliberation.
Your Brain on Heavy Metals.
This week in Neurochem we talked about a very controversial and growingly prevalent topic – autism. As most people know, autism is a disorder characterized by a difficulty in verbal/nonverbal communication, social interactions, relationships, and disinterest/extreme interest in various activities. And, interestingly, the disorder is becoming more and more prevalent. According to the article, “How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis,” by Deth et al. of Northeastern University, the incidences of autism have grown from 3 in every 10,000 children in 1970 to 66 in 10,000 children in 2002. This shocking increase has many people (especially mothers) wondering…why? What are we doing differently that is causing this drastic increase? While some attribute the increase to advanced diagnosis ability and awareness, it still leaves you wondering if there are other reasons as well.
When talking about the causes of autism, it’s hard not to mention the thimerosal debate. Thimerosal is an inorganic mercury compound that has been used as a preservative in vaccines since the 1930’s. In 1999, new research on the toxicity of thimerosal was conducted by the FDA, and, although research didn’t suggest anything to cause alarm, it was still decided to phase out thimerosal as a precautionary measure due to its structural relatedness to methylmercury.3 In 2000, parents of autistic children started forming groups based on the belief that vaccines had caused their children’s disorders. Although much research has disproved the thimerosal/autism link, the debate still lives on today.3
While thimerosal, a heavy metal derivative, seems not to cause autism, there is reason to believe that heavy metals could still be a culprit of the disorder. According to this week’s article, a redox/methylation hypothesis of autism is still a valid argument and explanation. This is based on the tendency of heavy metals to inhibit an important protein of sulfur metabolism, methionine synthase.
Homocysteine is an amino acid derivative of cysteine. In sulfur metabolism, HCY can be converted to three other molecules – S-Adenosyl-L-homocysteine (SAH), methionine (MET), or cystathionine, a glutathione precursor. In times of oxidative stress due to heavy metal exposure, most of this HCY is shunted to cystathionine production due to glutathione’s role as a powerful antioxidant. Essentially, methionine synthase is shut down to deal with more pressing issues – the oxidative stress. This leads to all sorts of effects for the cell.
One effect is SAH accumulation, since the reaction between HCY and SAH is reversible and no HCY is being utilized by methionine synthase. This inhibits two types of methylation reactions in the cell – DNA methylation and phospholipid methylation. DNA methylation is very important in turning certain genes on and off, so this can have astounding effects on the cell. Phospholipid methylation is related to dopamine release and neural synchronization which is responsible for attention and focus-related thinking skills. Genetic factors are very important in predisposing an individual in autism, however, they don’t totally cause autism, supporting this heavy metal hypothesis. Many genetic mutations and polymorphisms in autism appear in molecules related to this redox/methylation hypothesis.
Although the exact mechanisms of autism have yet to be elucidated, the redox/methylation hypothesis seems quite likely considering the joint environmental/genetic factors. Since it seems quite likely that the environmental part of autism could be causing the dramatic increase in cases seen in recent decades, further research in this area is in dire need. Furthermore, as rates increase, advocating for increased awareness about the disorder is desperately needed as well. Autism creates new educational/social challenges which will require novel methods of interpersonal interaction and treatment for these individuals.
http://www.morphonix.com/software/education/science/brain/game/specimens/wet_brain.html
http://www.boloji.com/index.cfm?md=Content&sd=Articles&ArticleID=1098
http://www.webmd.com/brain/autism/autism-symptoms
Deth, R., Muratore, C., Benzecry, J., Power-Charnitsky, V., and Waly, M. How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. Neurotoxicology 2008;29:190-201.
http://www.nationalautismassociation.org/thimerosal.php
Final Reflections
I enjoyed this Neurochemistry capstone course firstly, because of the interesting and fascinating topics that we covered. In the beginning part of the course, we discussed more of the biochemistry aspects and learned about different pathways, receptors, and substances within the human body that would provide us with a foundation for understanding the articles that were later to come. I don’t think that I would have gotten nearly as much out of the papers if we hadn’t discussed some of these pathways and mechanisms beforehand. The topics of the papers we discussed included concussions, addiction, obesity, bipolar, autism, and others. These were great articles to discuss because they covered a broad spectrum of disorders and they were also things that most of us have heard of and encountered at some point in our lives. However, I think that the most important skill I learned in this course is how to dissect these papers, and investigate different aspects of them in order to understand more about the whole picture. This will be a valuable skill as I continue my education and need to know how to investigate every aspect of a topic in order to fully understand it. Other aspects of this course such as the discussion of our individual areas of investigation, class discussions, and writing blog posts are all important skills to being a scientist. Concordia prides itself in “sending out thoughtful and informed individuals to influence the affairs of the world.” In order to be an effective scientist, one needs to share their area of expertise with other scientists, and know how to communicate their knowledge and discoveries both with other scientists and the general public. In this way, ideas and knowledge can be shared, and scientific advances and further discoveries can be made. This course has taught me how to do that through class discussions, investigations, and writing blog posts for the public to see.
Synchronized Dance Therapy for Autism
A new hypothesis in the cause of Autism is that of a dysfunctional motor neuron system. Motor neurons were discovered in the early 1990s while studying the brains of macaque monkeys. Researchers found that a group of neurons in the front part of their brains known as the ventral premotor cortex (just in front of the brain’s motor area) were activated when the monkey performed different tasks. The big shocker however, was that these same neurons were activated when the monkey watched someone else do the same action, just as if it had been doing the task itself. Much more research has been done since their discovery, and motor neurons are now known to be important to the tasks of empathy and socializing with other people, including communicating our emotions through facial expressions. In fact, it has been found that people with autism have dysfunctional mirror neuron systems. A characteristic of the disorder is difficulty socializing with others, and dysfunctional mirror neurons play a role in their inability to understand the intentions of others based on the action they observe. It has also been shown that the more severe the symptoms of autism are, the more inactive their mirror neurons are. The finding of these correlations has led to new therapeutic approaches that include autism patients imitating the actions of others.
V.S Ramachandran is a neuroscientist at the University of California, San Diego and is very well known and respected in the field of behavioural neurology. I have read is book: Phantoms in the Brain: Probing the Mysteries of the Human Mind that describes different neurological disorders, some of which are very rare and phenomenal, and how these “abnormalities” help us to understand how the brain is suppose to function under “normal” circumstances. I would highly recommend it to anyone fascinated by the mysteries of the human brain. Ramachandran has been studying this theory of autism that has come to be known as the “Broken Mirror” theory of autism. In a recent correspondence in Medical Hypotheses, Ramachandran and his colleague E.L. Seckel proposed a type of dance therapy for autism based on the theory that the mirror neuron system in autistic patients is not missing, but merely “dormant”. In Phantoms in the Brain, Ramachandran describes a therapy that he developed for patients with phantom limb involving mirrors. In a similar fashion, the therapy for autism that Ramachandran proposes is that an autistic patient would be in a room with multiple mirrors at different angles, and three neurotypical people. These people would dance to a rhythm and the autistic patient would mimic their movements and be able to watch themselves performing these actions in the many mirrors. In addition, Ramachandran and Seckel propose that various patterns of touch be administered to the autistic patient while they are watching themselves in the mirror, because of the existence of mirror neurons that fire when you watch someone else being touched. I would assume that the goal with this therapy is that the multiple ways to stimulate the mirror neurons would aim to restore the function of dormant mirror neurons in autistic patients.
This is a fascinating and novel therapy, and it will be interesting to see the future of therapies of this kind. Our paper with week was about the other pathways that may be a cause for autism. I think that future research should look at the theory of mirror neurons in conjunction with this article. Could the redox/methylation hypothesis be linked to these dormant mirror neurons, or can environmental factors impact mirror neurons in the same way that they can harm other pathways leading to autism? Findings about this link would also help to create combination treatments, which often seem to work better for many disorders, than one treatment alone.
For more information of mirror neurons and this new treatment, read the full articles that I have described, they’re very interesting!: http://www.sciencedirect.com.cordproxy.mnpals.net/science?_ob=MiamiImageURL&_cid=272414&_user=1822410&_pii=S0306987710004603&_check=y&_origin=search&_zone=rslt_list_item&_coverDate=2011-01-31&wchp=dGLzVlS-zSkzS&md5=499e9bc883e9a5c8121decf6c6450459/1-s2.0-S0306987710004603-main.pdf ; http://www.sfn.org/index.aspx?pagename=brainbriefings_mirrorneurons
Amyloid Beta Plaques: Destructive or Protective?
Contrary to popular “scientific” belief, we aren’t really that sure what causes the neurodegeneration of brain tissue in Alzheimer’s Disease (AD) patients. Thus, amyloid beta (AB) plaques are not nearly as deserving a scapegoat as is often thought.
If we investigate the chemical properties of AB depositions, we find that AB doesn’t exhibit the ability to make reactive oxygen species; rather AB exhibits anti-oxidant properties, implying that AB should be neuroprotective.
If AB is neurotoxic, we might expect to observe deleterious affects whenever AB production is increased, however AB increases are observed after instances of neuronal stress, as in cases of hypoglycemia and brain trauma. This result gives merit to the hypothesis: AB increases serve as a neuroprotective pathway due to physical stresses. So what is the role of AB plaques in the brain?
An alternative hypothesis to the origin of AB is that neuronal energy shortages coupled with Ca2+ overloads promote a fundamental switch in the metabolism route of Amyloid-Beta Precursor Protein (ABPP) from a non-amyloidogenic to an amyloidogenic pathway, i.e. it switches from the body making no AB plaques to the body making AB plaques. Since AB plaques show up after neuronal stress, induced by decreased energy production and higher Ca2+ concentrations (key symptoms exhibited by concussion patients), it appears that AB plaques play a protective role in the brain, and that ABPP is the necessary built-in protective system that is always on standby ready to create protective plaques.
So, even though AB plaques are always observed in AD patients, the presence of AB plaques is not unique to AD patients and thus is likely a bystander of the damaging effects of AD. Considering this information and that of the AD article we read, there are obviously mixed opinions regarding the role AB plays in AD. The article focused on in our neurochemistry course suggests that AB plaques are toxic, while other literature sources claim that AB is either a benign byproduct of AD or that it plays an active role in protecting the brain from the neurodegenerative nature of AD. Only future research will illuminate the true role AB plays in AD.
A Rotating Obsession: Autism Diagnosis and Treatment
As of 2002 autism affected 66 out of 10,000 people in the United States. With its growing prevalence, it is becoming even more important to get a proper diagnosis for autism so that the children can receive the best treatment available. Even though autism is not curable it can be managed and children can learn how to cope if therapy is introduced early. Autism is characterized by lack of social skills, impairments in communication or particular obsessions. Since a large part of autism is a lack of empathy, a lot of the therapy that is offered for autistic individuals is behavioral therapy.
I am personally affected by autism because my youngest brother who is now 17 years of age was diagnosed with Asperger’s, a subset of autism approximately 2 or 3 years ago. Asperger’s is not as severe as autism, and individuals with this disorder are very often viewed as normal individuals, they just don’t have as many social networks because they lack the capability to relate to others in the same capacity. My brother does lack some social skills, throughout elementary school and junior high school he was often made fun of for being different. But I think one of the most distinguishing characteristics looking back now was his obsessions. His obsessions often changed over the years, but during them he was totally and completely absorbed. During his toddler years he was totally and completely obsessed with Superman, for about a year and a half he even insisted that everyone call him Superman. The next phase of his obsessions was horses; he had imaginary horses that he would call to so they could follow us every time we drove anywhere. Next was Hotwheel cars, he had over 300 at one point. Then he started collecting fishing lures, which was an odd obsession because he hates eating fish, putting worms on the hook grossed him out, and he refused to take the fish off the line. As a 10 year old, his tackle box collection would make any seasoned fisherman jealous. His current obsession is archery, no one in our family has ever introduced him to bows and arrows, but he spent his entire summer working to make money to buy a very expensive bow to just practice with since he isn’t a hunter. Often times children have passions and hobbies, but few are as dedicated and committed to them as my brother, or other autistic individuals. Perhaps their dedication is something we should envy? To have such passion about something, anything, maybe we could accomplish so much more in life and have so much more depth to our learning.
The Cure for Alcoholism….
This week’s article was about alcohol abuse, alcoholism and the mechanisms behind it. The purpose of this article was to figure out what happens when alcohol enters the brain and what parts of the brain are affected. If scientists can figure out what happens, they may be able to find drugs that can reduce alcohol dependency in alcoholics, repair brain regions that have been damaged due to alcohol and even find drugs that can cause an aversion to alcohol. However, can there really be a cure for alcoholism?
Currently there are three drugs that are approved by the FDA for alcohol treatment. The first is called Campral and it is used to reduce the withdrawal symptoms experienced by long term alcohol abusers when they stop using. It is also believed that it helps the brain return to its normal cognitive function. However this drug has many side effects such as diarrhea, vomiting and nausea. Another drug is Antabuse and when this drug is taken in conjunction with alcohol, it causes headaches, nausea, vomiting, chest pain, sweating, choking and difficulty breathing. The last medication that has been approved is called Trexan, and it inhibits the “good feeling” that people get from drinking. The downsides of this drug are that it may worsen withdrawal symptoms from alcohol and it can only be used in treatment programs.
Although there are numerous drugs on the market, I don’t think that any one of them can really be used to treat alcoholism. I personally know a recovering alcoholic and after talking to her, she said that the only thing that really truly works is when the person wants to change, and is fully committed to making that change. She has been involved in Alcoholics Anonymous for three years now and even though there have been great struggles, it has been well worth the time. When I talked to her about easy fixes and the drugs that are now available to help, she is extremely skeptical on whether or not these drugs will work on the person long term. Sure you could easily take a drug that makes you puke when you drink, but people that truly desire the alcohol, will just not take the drug. The drug that improves your brain function, could be used as an excuse to just continue drinking, because in the end, you can take a pill and be cured from any brain damage.
Therefore in my opinion, alcoholism is not an easy fix. You can’t just magically take a pill and no longer desire alcohol. Recognize that you have a problem, desire change, and take action yourself to make those changes. We can’t always rely on medicine and science to fix our problems, the power rests in our own will.
If you are or known someone who is an alcoholic and would like more information about the program Alcoholics Anonymous, you can visit their website and find a meeting location near you by clicking here: http://www.aa.org/